EIF2B1
TRUNCATED 286 aa (canonical 305 aa) · UniProt Q14232 · CDLMPS
chr12:123632402:-:ATG:ENST00000424014.7
AI summary Truncation deletes a confidently-folded, packed N-terminal helix (res 3-16) that docks against the shared eIF-2B alpha domain core.
How it diverges
This truncation removes a 14-residue N-terminal helix (pLDDT 0.97) that makes 28 confident contacts with residues 20-56 of the shared core (mean PAE 2.2 Å), indicating it is a genuine packing element of the eIF-2B alpha N-terminal domain rather than a dangling appendage. No real InterPro domain boundary sits within the removed 19 aa (the eIF-2B alpha N-terminal domain begins at residue 15 and extends through the shared region), so annotated domain architecture nominally survives, but the structural evidence shows an integrated helical element is lost. The shared core itself does not refold (RMSD 0.91 Å at high pTM), so this is a clean subtraction of a packing helix, not a broader remodeling.
Why it matters
eIF2Bα is the regulatory subunit whose N-terminal domain forms the primary docking surface for phospho-Ser51 eIF2α, the interaction that confers stress-responsive translational shutdown and is the site competitively targeted by viral antagonists like SFSV NSs. Losing a packed N-terminal helix that sits just upstream of and contacts this eIF-2B alpha N-terminal domain plausibly compromises the structural integrity of that phospho-eIF2α docking surface or its assembly into the decamer, even though canonical domain boundaries (Pfam/CATH) are formally retained. This would functionally uncouple the isoform from stress sensing without necessarily abolishing basal GEF-independent activity, which does not require eIF2Bα.
LLM confidence medium
D3 mass-spec validation is absent and D1 ribo-seq support comes from a single cell line, so translation of this truncated start is not independently confirmed; disease-variant density in the removed region is nominally depleted relative to the shared core despite three ClinVar-pathogenic frameshift/nonsense alleles clustering there, making the region-level enrichment metric an unreliable summary of the concentrated loss-of-function signal.
Folding
Canonical (305 aa)
Download CIF
Isoform (286 aa)
Download CIF
Coloured by ESMFold2 pLDDT confidence (blue = high, orange/red = low).
Differential region — residues 1–19 (lost from canonical) — recoloured on a yellow→purple pLDDT ramp so it stands out.
Drag to rotate · scroll to zoom · download a CIF to explore in your own viewer.
Canonical PAE
Isoform PAE
Predicted aligned error: expected Cα error (Å) at residue j when the fold is superposed on residue i. Dark = confident relative placement; bright = uncertain.
The dashed outline marks the differential region (1–19).
Evidence — click any tile for the differential-region detail
C
Conservation
Interesting
LLM reasoning
The N-terminal segment removed by this truncation is under strong purifying selection, arguing its loss is functionally consequential rather than neutral. Primate amino-acid identity over the region is 97.7% (essentially matching the canonical protein's own 98.8% baseline), and mammalian identity is 93.4%, close to the canonical 96.0% baseline, indicating this stretch is conserved to a similar degree as the rest of the protein rather than being a fast-evolving patch. Absolute phyloP over the unique region is 3.40, well above the ~2 strong-constraint threshold, and comparable to the shared region's 3.68, confirming base-level purifying selection independent of amino-acid identity. Together these three signals converge on the same conclusion: the truncated N-terminal segment is evolutionarily constrained, so its removal likely has real functional impact rather than being tolerated variation.
Unique region 97.7% similar across primates
How well is the isoform-unique region conserved at the amino-acid level across primates (mean percent identity)? High AA identity in close relatives argues the alternative protein is real and translated, not a sequencing or annotation artifact. (Reading-frame intactness is shown as context.)
Comparison
Sequence conservation · primate
mean AA identity over the differential ORF is the score basis; frame intactness across the clade is context
| Conservation metric | Canonical ORF | Differential ORF |
|---|---|---|
| Mean AA identity | 99% | 98% |
| Frame intact (fraction of species) | 96% | 100% |
| Species aligned | 25 | 25 |
| Species frame-intact | 24 | 25 |
| Start codon conserved | 100% | 100% |
| Deepest intact species | Microcebus_murinus | Microcebus_murinus |
| Phylo depth (MRCA) | 7 | 7 |
Unique region 93.4% similar across mammals
The same amino-acid identity test across mammals. Conservation over deeper evolutionary distance is stronger evidence the ORF is under selection to be translated. (Reading-frame intactness is shown as context.)
Comparison
Sequence conservation · mammalian
mean AA identity over the differential ORF is the score basis; frame intactness across the clade is context
| Conservation metric | Canonical ORF | Differential ORF |
|---|---|---|
| Mean AA identity | 96% | 93% |
| Frame intact (fraction of species) | 80% | 95% |
| Species aligned | 20 | 20 |
| Species frame-intact | 16 | 19 |
| Start codon conserved | 100% | 100% |
| Deepest intact species | Loxodonta_africana | Loxodonta_africana |
| Phylo depth (MRCA) | 12 | 12 |
Unique region PhyloP: 3.40 — purifying selection
phyloP / phastCons measure per-base evolutionary constraint. A high absolute phyloP over the differential region means the sequence itself is under strong purifying selection — evidence it is coding and does something. (Enrichment over the shared core is shown as context only.)
Comparison
Per-base conservation · differential region
absolute mean phyloP over the differential region is the score basis (high = strong purifying selection); the shared column and enrichment are context, not the claim
| Track | Differential | Shared | vs shared |
|---|---|---|---|
| phyloP mean | 3.4 | 3.68 | 0.925 |
| phastCons mean | 0.849 | 0.834 | — |
Start site · canonical vs isoform
initiation context + per-base conservation at each start codon
| Property | Canonical | Isoform |
|---|---|---|
| Start codon | ATG | ATG |
| Kozak context (−9..+4) | GAGGACGCCATGG | GATCCTGACATGG |
| phyloP at start codon | 6.94 | 2.47 |
| phastCons at start codon | 1 | 1 |
| phyloP over Kozak window | 2.68 | 3.32 |
| phastCons over Kozak window | 0.761 | 0.998 |
| Kozak mismatch — full consensus | 3 | 5 |
| Kozak window GC content | 0.692 | 0.538 |
D
Detection
Neutral
LLM reasoning
This truncated isoform's alternative start site has weak, single-source ribosome-profiling support and no proteomic confirmation. Start-site usage is only detected in 1 of 6 cell lines (HeLa), with initiation efficiency 0.029 versus canonical initiation efficiencies of 0.016-0.155 across other lines (K562, U2OS, RPE1) — comparable in magnitude but from a different cell-line panel, so it does not corroborate the same site being used broadly. No unique peptides were validated by mass spec (0/4 isoform-unique peptides), so there is no independent proteomic confirmation that the truncated N-terminus is translated. Overall this is thin, single-condition ribo-seq evidence with no orthogonal confirmation, which is unremarkable rather than a red flag against the isoform.
detected in 1/6 cell lines
Is the alternative start used in more than one cell line? Reproducible initiation across independent samples argues against a one-off ribosome artifact.
Comparison
Per-cell-line usage · canonical vs isoform
Fisher q = 4.19e-06
| Cell line | Canonical | Isoform | p-value |
|---|---|---|---|
| HeLa | — | 2.73 | 4.19e-06 |
| K562 | 22.6 | — | — |
| U2OS | 2.21 | — | — |
| RPE1 Async | 1.09 | — | — |
| RPE1 Que | 0.676 | — | — |
Max Initiation Efficiency: 0.029
How efficiently ribosomes initiate at this start (TIS) relative to background, per cell line. Strong, reproducible initiation supports a genuine translation event.
Comparison
Start-Site Usage · canonical vs isoform
ribosome initiation efficiency at the canonical start vs this alternative start, per cell line
| Cell line | Canonical | Isoform |
|---|---|---|
| HeLa | — | 0.029 |
| K562 | 0.155 | — |
| U2OS | 0.0239 | — |
| RPE1 Async | 0.0194 | — |
| RPE1 Que | 0.0189 | — |
0/4 isoform-unique peptides validated
Were tryptic peptides unique to the differential region detected by mass spec? Direct peptide evidence is the strongest proof the isoform protein exists.
Comparison
Peptide Evidence (canonical vs isoform)
isoform-unique peptides are direct evidence the alternative protein exists
| Feature | Canonical | Isoform |
|---|---|---|
| Tryptic peptides (in-silico) | 40 | 4 |
| Validated by mass-spec | 0 | 0 |
| Isoform-unique peptides | — | 4 |
Details
Peptide Evidence (canonical vs isoform)
- peptide MASAVAAIR 0–9
- peptide ASAVAAIR 1–9
- peptide MASAVAAIRTLLEFLK 0–16
- peptide ASAVAAIRTLLEFLK 1–16
L
Localization
Not interesting
LLM reasoning
Removing the N-terminal 19-aa segment does not alter predicted subcellular fate: DeepLoc calls both canonical and truncated isoform Cytoplasm|Nucleus with near-identical top probabilities (0.705 vs 0.711), and the same nuclear localization/export signals and soluble membrane status are retained in both. SignalP and TargetP likewise show no change, with both canonical and isoform classified as no secretory signal / no transit peptide (probability deltas negligible, <0.007). No evidence here suggests the truncation shifts compartmentalization or targeting.
iso: Cytoplasm, Nucleus | canon: Cytoplasm, Nucleus
Do the predicted localization features (DeepLoc prediction, sorting signals, or membrane association) differ between the canonical and the isoform? A protein with changed localization features acts in a different cellular context.
Comparison
Subcellular localization (DeepLoc)
no localization-feature change
| Property | Canonical | Isoform |
|---|---|---|
| Predicted location | Cytoplasm|Nucleus | Cytoplasm|Nucleus |
| Sorting signals | Nuclear localization signal|Nuclear export signal | Nuclear localization signal|Nuclear export signal |
| Membrane | Soluble | Soluble |
iso: noTP | canon: noTP
Do N-terminal targeting signals (SignalP secretion, TargetP mitochondrial/chloroplast) differ between canonical and isoform? N-terminal changes most directly add or remove targeting peptides.
M
Mutation Landscape
Interesting
LLM reasoning
The 19-residue segment removed by this truncation (canonical residues 1-19) is a tight loss-of-function hotspot, not a diffuse or quiet region: despite being only 57 nt long, it hosts 45 variant records including a start-loss variant at Met1 itself (p.Met1?, ESM-C LLR -6.96) and three ClinVar-pathogenic frameshift/nonsense calls (p.Tyr9fs, p.Lys11Ter, p.Met14fs) that sit on just three residues, matching 100% of the top-10-position mass in the pathogenic histogram (residue span 8-13). A COSMIC stop-gained (Glu8Ter) and additional gnomAD-catalogued frameshift/nonsense alleles cluster at the same 7-13 stretch, and the missense variants nearby carry high AlphaMissense scores (0.87-0.97). This corroborates that ablating this N-terminal segment (which contains the canonical initiation codon) is a recurrent, multi-database route to loss of function, even though the region-level disease enrichment ratio (0.72) undersells it by diluting a small absolute count (13) over a tiny denominator. The germline constraint signals were themselves ambiguous (gnomAD depletion ratio 1.09 ~neutral, ESM-C constraint enrichment 1.79 just under the 2.0 threshold) so they don't independently drive the call, but the positional clustering of disease-relevant loss-of-function variants right at the alternative-isoform-defining start region is a strong, tool-verified signal the summary ratios could not express.
gnomAD variants comparable in unique region — neutral
Does healthy human germline variation (gnomAD) avoid this region (depletion ratio < 1×), and is it intrinsically constrained (ESM-C constraint delta > 0)? Depletion of population variation plus high sequence constraint mean the region resists change — it is functionally important. Scored only where the unique region is canonical coding sequence, i.e. on truncations. gnomAD is a tolerance catalogue, not a disease one; disease/cancer variants (ClinVar / COSMIC) live in M2.
Comparison
Germline Variants · differential vs shared region
gnomAD (population) variant density per nucleotide — depletion ratio < 1× means healthy human variation avoids the region (constrained), the M1 basis alongside ESM-C constraint
| Variant set | Differential | Shared | Depletion ratio |
|---|---|---|---|
| gnomAD variants | 32 | 440 | 1.1× |
Sequence constraint (ESM-C) · differential vs shared region
lower LLR = more constrained; enrichment = differential / conserved
| Property | Differential | Shared | Enrichment |
|---|---|---|---|
| ESM-C mean LLR | -0.691 | -0.386 | — |
| Constrained positions | 0 | 3 | — |
Predicted-damaging variants · germline (gnomAD)
AlphaMissense / ESM-C / LoF calls per region (length-normalized)
| Variant set | Differential | Shared | Enrichment |
|---|---|---|---|
| Scorable variants | 31 | 435 | 1.1× |
| Damaging variants | 8 | 145 | 0.83× |
| — of which loss-of-function | 6 | 38 | 2.4× |
| AlphaMissense-pathogenic | 2 | 102 | 0.3× |
Predictor scores · germline (gnomAD)
scored: 673 ESM-C · 411 AlphaMissense
| Property | Differential | Shared |
|---|---|---|
| Mean ΔLLR (ESM-C) | -3.13 | -3.63 |
| Min ΔLLR (ESM-C) | -9.11 | -12.3 |
| Mean AlphaMissense | 0.216 | 0.475 |
Disease variants 1.38× less in unique region — depleted
Are disease (ClinVar / COSMIC) variants enriched per nucleotide in the differential region versus the shared core (disease enrichment ratio ≥ 1×)? Disease variants concentrating in the unique region tie it to phenotype.
Comparison
Clinical-variant burden · differential vs shared region
counts per region; ratio is density-normalized (variants per nucleotide, differential ÷ shared — ≥1× = disease variants concentrate in the differential region, the M2 basis)
| Variant set | Differential | Shared | Enrichment |
|---|---|---|---|
| Disease variants | 13 | 270 | 0.72× |
| Pathogenic | 3 | 30 | 1.5× |
Predicted-damaging variants · disease (ClinVar/COSMIC)
AlphaMissense / ESM-C / LoF calls per region (length-normalized)
| Variant set | Differential | Shared | Enrichment |
|---|---|---|---|
| Scorable variants | 13 | 266 | 0.74× |
| Damaging variants | 5 | 79 | 0.95× |
| — of which loss-of-function | 4 | 24 | 2.5× |
| AlphaMissense-pathogenic | 1 | 52 | 0.29× |
Predictor scores · disease (ClinVar/COSMIC)
scored: 673 ESM-C · 411 AlphaMissense
| Property | Differential | Shared |
|---|---|---|
| Mean ΔLLR (ESM-C) | -3.31 | -3.21 |
| Min ΔLLR (ESM-C) | -5.67 | -12.2 |
| Mean AlphaMissense | 0.269 | 0.478 |
P
Predicted Structure
Interesting
LLM reasoning
This truncation deletes a confidently-folded, load-bearing N-terminal helix. The removed region (canonical residues 1-19) contains a 14-residue helix (residues 3-16) at pLDDT 0.97, well above the fold-confidence and length thresholds. Contacts from this helix concentrate on a small set of nearby residues (20, 25, 29, 33, 52, 55, 56 — 28 contacts among 14 partner residues), indicating a genuine packing interface rather than scattered surface contacts, and the mean PAE between the helix and the rest of the canonical structure is only 2.2 Å, meaning it is confidently and tightly placed against the core, not a dangling well-folded fragment. The shared-region RMSD is negligible (0.91 Å, TM-score 0.99) against a high global pTM (isoform 0.94, canonical 0.96), so there is no confounding refold signal — this is a clean, high-confidence loss of an integrated structural element.
pLDDT Differential Region:
0.963
Does the gained/lost region fold into ordered structure (pLDDT) and shift the protein's biophysical character (charge, hydropathy, disorder)? Structured, biophysically distinct regions are more likely to be functional.
Comparison
Structure (ESMFold2) · canonical vs isoform
TM-score 0.956 · RMSD 0.835 Å
| Metric | Canonical | Isoform |
|---|---|---|
| pLDDT (whole protein) | 0.943 | 0.93 |
Fold confidence · differential vs shared region
mean ESMFold2 pLDDT in each region
| Metric | Differential | Shared | Enrichment |
|---|---|---|---|
| pLDDT | 0.963 | 0.974 | 0.99 |
Shared-Region RMSD:
0.91 Å
The shared region is the stretch of protein identical in both the isoform and the canonical (the canonical body for an extension; the post-truncation body for a truncation). Folded in both contexts it normally comes out nearly identical, so its Cα backbone RMSD ≈ 0. A high shared-region RMSD (superposed on the shared residues only, from the ESMFold2 structures) means the extension or truncation reorganizes how the retained region folds — a rare, high-interest functional signal. TM-score is a length-normalized companion; the check only fires when both structures are confidently folded, and uORF/altORF isoforms (no shared region) are not evaluable.
Comparison
Shared-region structural change
Cα RMSD superposed on the shared residues only; TM-score is length-normalized · shared-region Cα RMSD 0.908 Å · shared TM-score 0.986 · shared region 286 aa · min shared pLDDT 0.93 · global TM-score 0.956 · global RMSD 0.835 Å
| Property | Canonical | Isoform |
|---|---|---|
| Shared-region pLDDT | 0.942 | 0.93 |
1 secondary structure identified in unique region
Does the differential region contain actual secondary structure — a helix or strand — rather than coil? ESMFold2 predicts coordinates but no secondary structure, so elements are assigned from those coordinates (P-SEA, Cα geometry). Because they are derived from a prediction, each element carries its own mean pLDDT: a geometrically clean helix running through a disordered stretch is geometry fitted to a guess, so BOTH length and confidence are required to score. The direction differs by ORF type — an extension GAINS the element (a candidate functional addition), a truncation LOSES one, and there the element is read off the canonical structure because the removed segment exists only in it. This says nothing about whether the element is integrated with the rest of the fold; the contact and PAE evidence in this same category answers that.
Comparison
Secondary structure · differential vs shared region
helices and strands assigned from the predicted coordinates (P-SEA)
| Metric | Differential | Shared |
|---|---|---|
| Alpha helices | 1 | 8 |
| Beta strands | 0 | 2 |
| Longest element (aa) | 14 | 29 |
| Mean pLDDT | 0.97 | 0.97 |
Elements and coordinates
1 in the differential region, 10 in the shared core — residue numbering is 1-based on the protein holding the region
| Removed (canonical) | Shared core |
|---|---|
| alpha helix 3–16 14 aa · pLDDT 0.97 | alpha helix 22–36 15 aa · pLDDT 0.97 |
| — | alpha helix 42–59 18 aa · pLDDT 0.96 |
| — | alpha helix 63–77 15 aa · pLDDT 0.93 |
| — | alpha helix 86–114 29 aa · pLDDT 0.95 |
| — | beta strand 122–127 6 aa · pLDDT 0.99 |
| — | alpha helix 132–144 13 aa · pLDDT 0.98 |
| — | alpha helix 160–171 12 aa · pLDDT 0.98 |
| — | alpha helix 211–222 12 aa · pLDDT 0.98 |
| — | beta strand 223–230 8 aa · pLDDT 0.99 |
| — | alpha helix 295–304 10 aa · pLDDT 0.95 |
Below threshold
0 in the differential region, 5 in the shared core — shorter than 6 aa or below pLDDT 0.70, so not counted above
| Removed (canonical) | Shared core |
|---|---|
| — | beta strand 148–152 5 aa · pLDDT 0.98 |
| — | beta strand 174–178 5 aa · pLDDT 0.98 |
| — | beta strand 205–207 3 aa · pLDDT 0.99 |
| — | beta strand 273–276 4 aa · pLDDT 0.98 |
| — | beta strand 283–285 3 aa · pLDDT 0.99 |
S
Structural Characteristics
Not interesting
LLM reasoning
None of the three structural-characteristics submodules found a meaningful shift for this truncation, which removes a 19-aa N-terminal segment of the canonical eIF2B1 protein. No real InterPro domain overlaps the removed region (the eIF-2B alpha N-terminal domain and Pfam/PANTHER/SUPERFAMILY hits all sit within the retained shared sequence, e.g. spanning residues 15-305/304), so domain architecture is intact in the truncated isoform. The whole-protein biophysical shift is negligible (gravy delta 0.10, fraction-charged delta -0.017, disorder delta -0.008), well under any threshold for a distinct shift despite the removed 19-mer itself looking more charged/disordered than the shared core. The sparse-autoencoder magnitude check also falls short of threshold (top shared-feature activation shift 8.09 vs a 10.0 cutoff), so despite hundreds of gained/lost features between the two proteins (53 vs 81, expected given the length difference), no single feature shift is large enough to flag a real change. Together this argues the truncation removes a short segment without disrupting annotated domains, bulk biophysical character, or strongly activating any interpretable sequence/structure feature.
No diverging domains
Does the isoform gain or lose a real InterPro functional domain in the differential region (disorder/structural-only signatures excluded)? Gaining or losing a domain changes function directly.
Comparison
Domains & motifs (canonical vs isoform)
gained = only in the isoform; lost = only in the canonical
| Feature | Canonical | Isoform |
|---|---|---|
| InterPro domains | 7 | 7 |
| Short linear motifs | 3 | 3 |
less hydrophobic (-1.68) · more charged (+0.28) · more disordered (+0.13)
Biophysical character of the isoform-differential region versus the shared canonical core — pI, hydropathy, charge, disorder and related properties. Descriptive; the folding (P1) score keys off the GRAVY / charge / disorder deltas.
Comparison
Biophysics · differential vs shared region
highlighted rows are enriched in the differential region
| Property | Differential | Shared | Enrichment |
|---|---|---|---|
| Isoelectric point (pI) | 3.85 | 8.58 | 0.449 |
| Hydropathy (GRAVY) | -1.5 | 0.179 | -8.39 |
| Fraction charged | 0.526 | 0.245 | 2.15 |
| Disorder fraction | 0.188 | 0.0542 | 3.46 |
| Disorder-promoting | 0.684 | 0.514 | 1.33 |
| Low-complexity fraction | 0 | 0.0874 | 0 |
| Prion-like fraction | 0.158 | 0.213 | 0.74 |
| LLPS score | 0.118 | 0.123 | 0.959 |
| π–π propensity | 0.158 | 0.189 | 0.836 |
| Aromaticity | 0.105 | 0.0769 | 1.37 |
| Instability index | 36.5 | 30.1 | 1.22 |
| Shannon entropy | 3.22 | 4.05 | 0.796 |
| Normalized complexity | 0.758 | 0.936 | 0.81 |
134 SAE features differ
Sparse-autoencoder (SAE) interpretability features on the ESM-C residual stream, comparing the isoform against the canonical protein. This is the S3 criterion — a presence check that fires when any interpretable feature is gained or lost. Only the top 30 features per category (ranked by activation, prevalence ≥ 2) are saved; each table shows the top 10 interpretable features, and generic / "unknown" features are hidden unless you expand it. What are SAE features? →
Part 1 · Global feature comparison
Which SAE features fire in the isoform vs the canonical protein, across the whole sequence.
Isoform-only features — 53 total (prevalence ≥ 2)
| Feature | Label | Description | Activation | Prevalence |
|---|---|---|---|---|
| #14542 | bHLH helix-1 amphipathic segment | Short amphipathic α‑helical segments at helix–loop (helix–helix) boundaries, most characteristically the N‑terminal helix (helix 1) of basic helix‑loop‑helix (bHLH) hairpins; the feature favors mixed basic/polar and small/hydrophobic residues along one helical face and also fires on analogous short helices immediately following a coil break in non‑TF proteins. | 5.35 | 2 |
| #1162 | Short amphipathic interface helices | Short amphipathic alpha‑helical surface patches that serve as generic macromolecular interface elements (often contacting DNA/RNA or protein partners and frequently flanking/including catalytic acidic residues or metal‑binding positions) | 4.40 | 2 |
| #14603 | Charged amphipathic interaction helices | Charged, amphipathic alpha‑helical interaction segments—often N‑terminal and coiled‑coil‑like—that mediate protein–protein or protein–membrane contacts in small complex subunits and diverse enzymes/membrane proteins across taxa | 3.75 | 2 |
| #719 | Hydrophobic alpha-helical packing residues | Hydrophobic alpha-helical packing residues: the feature marks apolar positions within long, well-formed alpha-helices (both transmembrane segments and soluble/coiled-coil helices), capturing helix-core/face packing rather than specific catalytic motifs. | 3.55 | 3 |
| #512 | Short functional domain segments | Short sequence segments distributed across diverse proteins, with peaks that often fall within structured catalytic, transporter, or fold-defining domains as well as occasional acidic/charged stretches and flexible linkers. | 3.51 | 8 |
| #9254 | Alpha1 hydrophobe at glycine-loop | Hydrophobic residue at the entry helix of a nucleotide-binding pocket (beta1–alpha1 region), typically immediately C‑terminal to a glycine-rich loop; most commonly in Rossmann NAD(P)-dependent dehydrogenases (notably SDR and related oxidoreductases) and analogously positioned in E1-like adenylate-forming enzymes (e.g., MoeB/MOCS3). | 2.93 | 2 |
| #2080 | AAA+ helical interaction hotspots | Short, residue-level hotspots on conserved alpha-helical elements of AAA+ ATPase domains (notably HslU/ClpY unfoldases), with peaks falling on two characteristic motifs — an N-terminal "AIALRNR"-like helix near the ATP-binding lobe and a C-terminal "HT[IVM][LM]E[RK]L"-like helix — as well as occasional firing on sigma factors and other alpha-helical interaction modules. | 2.78 | 2 |
| #7726 | Amphipathic helical interaction motifs | Amphipathic alpha‑helical interaction motifs in eukaryotic regulatory proteins—most prominently the helices of the helix‑loop‑helix/basic HLH region, but also short helical binding elements such as PAS-domain helices, BH3 motifs, IQ/calmodulin‑binding helices, and helices within helical catalytic folds (e.g., Sec7)—enriched in basic and hydrophobic residues and used for DNA binding, dimerization, and protein–protein recognition. | 2.74 | 2 |
| #14382 | uL18 LDxGL motif | A conserved sequence/structural microsite in the large ribosomal subunit protein uL18 (L5) family, centered on a "LD(V/A/I/T)GL" motif around residue ~149, with occasional activation on analogous short strand-following loop segments in other folds. | 2.72 | 2 |
| #3991 | AAT-fold PLP-binding core | PLP-dependent aspartate aminotransferase–fold enzymes (class I/II): the feature recognizes the conserved active-site core within the AAT domain, firing in regions of the substrate/PLP-binding cleft of the large catalytic domain; it fires across diverse AAT-superfamily subclasses including aminotransferases, alpha-oxoamine synthases, many PLP decarboxylases, and C–S lyases involved in amino acid, one-carbon/glycine, lipid, cofactor, and specialized metabolite pathways in all domains of life. | 2.71 | 2 |
| #13118 | Alpha-solenoid and coiled-coil scaffolds | Alpha-helical repeat scaffolds in large eukaryotic proteins—principally HEAT/ARM-like alpha‑solenoids and long coiled‑coil rods used as assembly/tethering frameworks in nuclear transport, nucleoporins, and vesicle/endomembrane trafficking; the feature emphasizes structured helices and their termini rather than specific sequence motifs. | 2.53 | 3 |
| #2600 | Eukaryotic regulatory helical modules | Ordered structured modules in eukaryotic regulatory and signaling proteins, with strongest activation on small helix-containing folds — including SANT/Myb-like domains in chromatin remodelers and EF-hand calcium-binding domains — and on associated helical/scaffolding elements within these proteins. The feature emphasizes residues within ordered modules rather than catalytic ATPase or DNA-contact sites, and appears across diverse eukaryotes. | 2.46 | 3 |
| #2988 | SAM-binding motif I loop | Short conserved loop adjoining the S-adenosyl-L-methionine (SAM) cofactor pocket in Class I AdoMet-dependent enzymes—predominantly methyltransferases—corresponding to the motif I/post‑I beta-hairpin/loop that helps position/bind SAM (often Gly/Pro/Asp-enriched) and borders catalytic residues | 2.38 | 2 |
| #4856 | Phosphate/oxyanion-binding catalytic motifs | Conserved phosphate/oxyanion-binding catalytic-loop motifs, most often the nucleotide-binding signatures of ATP/NTP-dependent enzymes (Walker A KT threonine of P-loop NTPases and the paired N/G1 boxes of the GHKL/HATPase_c fold in histidine kinases), with analogous peaks at nearby catalytic/reactive residues in related enzymes (e.g., P-type ATPases) and at DNA phosphate–binding hairpins in DNA repair glycosylases; in some soluble enzymes (e.g., HemD, cyclins) the signal extends across the core that positions these sites. | 2.35 | 3 |
| #4919 | Alpha-helical gene-regulatory domains | Compact alpha-helical recognition domains, primarily ALOG-domain plant transcription factors and chromatin-reader bromodomains, with additional activation on helical segments of other nuclear gene-regulatory proteins (Homeobox, HMG box, Myb, ARID) and helical protein–interaction modules (UBZ zinc fingers, BTB) in nuclear scaffolds and co-regulators. The feature also fires on certain N-terminal helical segments of beta-amylase enzymes. | 2.33 | 4 |
| #4777 | Positive-inside TM helix interface | Transmembrane α-helical segments and their cytosolic interface in multi-pass membrane proteins, especially inner-membrane systems (mitochondria, chloroplast/thylakoid, ER). The feature keys on a single hydrophobic TM helix together with the immediately preceding cytoplasmic region, with strong basic (Lys/Arg) clusters consistent with the positive-inside rule. It often highlights pore/gating or helix-packing segments used by channels, transporters, and insertases. | 2.25 | 2 |
| #13781 | TIR/SEFIR BB-loop hinge | Conserved β-strand–loop–α-helix hinge of the TIR/SEFIR fold (the βB–αB “BB-loop” and adjacent helix), typically hydrophobic and often bearing a Trp–Cys (WC) signature; at lower specificity the feature generalizes to compositionally similar, glycine/proline‑rich β→loop→α hinges in unrelated enzymes | 2.22 | 2 |
| #5063 | Motif I SAM-binding loop | Conserved SAM/SAH-binding loop (motif I) of class I Rossmann-like S-adenosylmethionine-dependent methyltransferases: the short, often glycine-rich beta-to-alpha connecting loop that binds the SAM phosphate-ribose near the active site | 2.21 | 2 |
| #3432 | Charged helix-cap loops | Short, charged/polar, low‑complexity loop and linker segments that flank or interrupt alpha‑helical bundles—most prominently at disordered‑to‑ordered boundaries and helix–coil junctions of Dbl homology (RhoGEF) domains, but also in BAR coiled‑coils and four‑helix cytokines—often splice‑variable and enriched in E/D/K/R/S/T and prolines, with occasional peaks at the starts of small domains (e.g., FYVE) | 2.18 | 2 |
| #13571 | ATP-adjacent helix-loop-beta lid | A conserved helix–loop–β module that forms one wall/lid of the active‑site cleft in ATP‑utilizing catalytic domains, especially in ATP‑grasp/amide‑ligase folds and atypical kinase folds; the feature tags this ordered subsegment adjacent to the nucleotide pocket rather than the canonical ATP/Mg2+ signature motifs. | 2.17 | 2 |
| #6466 | C-terminal scaffold interaction surfaces | Structured C-terminal portions of repeat-based eukaryotic scaffold domains—specifically the last few repeats and their inter-repeat linkers in WD40 β-propellers and helical-repeat solenoids (PUM/PCI/ARM/HEAT/TPR), plus the C-terminal helix–loop–helix of EF-hand pairs—and, additionally, the terminal β-strands/loops of outer mitochondrial β-barrel channels (e.g., TOM40)—that constitute exposed interaction surfaces for partner/substrate binding and oligomerization; these segments are compositionally enriched in small hydrophobics with scattered acidic residues. | 2.16 | 2 |
| #4173 | Conserved BAH domain segments | A BAH (Bromo-Adjacent Homology) domain feature that marks conserved internal segments of BAH domains in eukaryotic chromatin/DNA-associated proteins, including DNA cytosine-5 methyltransferases, origin recognition complex subunits, and related chromatin readers. | 2.16 | 4 |
| #11257 | Phosphate-binding amphipathic helix | Short amphipathic alpha-helical segment that frequently serves as the phosphate-/nucleotide-binding helix immediately C-terminal to a glycine-rich phosphate-binding loop (P-loop or Rossmann-like), stabilizing ATP/ADP, nucleotide-sugar, or FAD/FMN pyrophosphate groups; when no such ligand is used, the feature selects a similar N-terminal helix with the same physicochemical profile. | 2.15 | 2 |
| #14065 | Extended C-terminal tail region | In a subset of proteins, long, contiguous C-terminal domains/tails are tracked; the feature marks the final functional region of the polypeptide (often hydrophobic and Gly/Ala-rich) when such an extended C-terminal segment is present, rather than a specific short motif. This is not universal across the represented enzyme families. | 2.14 | 3 |
| #10159 | HEAT/ARM alpha-solenoid repeats | Alpha-solenoid HEAT/Armadillo–like helical repeat scaffolds; the feature marks the helices (and adjacent helix–loop junctions) that build tandem HEAT/ARM/adaptin-like repeats used as non-enzymatic interaction platforms across trafficking, nuclear transport, chromatin organization, splicing, cytoskeletal regulation, and mTOR signaling, and also fires on smaller prokaryotic HEAT-repeat proteins. | 2.11 | 2 |
| #2844 | Active-site capping loop | Short proline/glycine–enriched turn/loop segments at secondary-structure junctions (often containing PP or GPP motifs), typically capping a beta strand or initiating an alpha helix and frequently positioned next to functional sites (e.g., metal-/cofactor-binding His/Asp/Glu or substrate/proline-binding pockets). This marks flexible, active-site–adjacent or gating loops reused across many folds, with occasional extension into the adjoining strand/helix residue. | 2.11 | 2 |
| #1679 | DXPS C-terminal glycine-rich loop | A conserved glycine/basic-rich loop in the C-terminal domain of ThDP-dependent 1-deoxy-D-xylulose-5-phosphate (DXP) synthases and related transketolase-family carboligases. | 2.10 | 2 |
| #6800 | 7TM membrane helix bundle | Membrane-embedded alpha-helical bundle segments of multi-pass proteins, with strongest preference for seven-transmembrane (7TM) architectures (GPCR/rhodopsin-like receptors, SWEET/PAQR-type receptors/transporters, TLC-domain proteins, viral gM and related heptahelical sensors), capturing adjacent helix pairs/triads characterized by helix–helix packing motifs (small-residue patterns and aromatic anchors). | 2.08 | 2 |
| #13767 | Non-catalytic coupling helices | Non-catalytic alpha-helical coupling and interface elements of nucleotide-dependent molecular machines and regulators (P-loop NTPases/AAA+ systems, translation GTPases, ATP synthase, RNA/DNA polymerases/helicases, and type II topoisomerases; also small GTPase regulatory complexes such as Arf/ArfGAP). The feature emphasizes structured helices that transmit conformational changes and mediate oligomer/substrate contacts, while generally avoiding the Walker A/P-loop and other catalytic residues. | 2.05 | 2 |
| #5187 | Nucleotide-sugar donor-binding site | Catalytic donor nucleotide-activated moiety binding site of glycosyltransferases and closely related nucleotide-dependent transferases, i.e., the short active-site segments that coordinate the nucleotide-linked donor (UDP/GDP/CMP/CDP/ADP) and perform transfer. The feature focuses on histidine flanked by acidic residues and nearby aromatics that form the donor pocket, aligning with family signature motifs such as DXD (metal-binding) in GT-A, the PSPG box in GT-B (UGT family), sialylmotifs in sialyltransferases, and analogous motifs in CDP-glycerol glycerophosphotransferases involved in teichoic acid biosynthesis. | 2.04 | 3 |
Canonical-only features — 81 total (prevalence ≥ 2)
| Feature | Label | Description | Activation | Prevalence |
|---|---|---|---|---|
| #6997 | Acidic/glycine interface loops | Surface-exposed loop/turn positions—especially beta-strand–connecting hairpins and helix↔sheet junctions—enriched in Asp/Glu and/or Gly (often short Gly-rich motifs), including the canonical glycine-rich AdoMet/S-adenosylmethionine binding loop; these mark interface/cofactor-recognition loops in beta-rich extracellular folds (cupredoxin/plastocyanin-like, TNF) and enzymes, rather than metal-binding sites. | 12.17 | 2 |
| #3609 | Position-2 N-terminus residue detector | Detector of the identity of the second residue at the extreme N-terminus of proteins, with strongest preference for small residues (especially Ser, Ala, and Gly; also Thr/Pro), i.e., an N-terminal position-2 signal commonly associated with generic, disordered starts and co-translational N-terminus processing | 7.86 | 2 |
| #2530 | LTV1/MPP10 motifs, TruD helix | Sequence-specific motif feature active in ribosome/snoRNP biogenesis factors and TruD-family pseudouridine synthases. In LTV1 homologs the feature recognizes a conserved internal "SSVxRRNEQL"-like motif, and in MPP10 homologs it recognizes a conserved "P(A/V)PVITEE" motif. In TruD/PUS7-family proteins it activates along an internal alpha-helix within the TRUD catalytic domain. | 6.99 | 3 |
| #4663 | Helical hydrophobic-aromatic binding motif | Conserved hydrophobic-aromatic motifs embedded in functional protein-protein and cofactor-binding sites, including the [4Fe-4S] cluster-binding region of archaeal DNA primase large subunit (PriL) and the CDK-binding "Speedy/Ringo box" of Speedy proteins | 6.21 | 15 |
| #11969 | Sparse motif hotspot detector | Punctate residue-level detector that fires at a small number of sites per protein, recurring on conserved sequence motifs in specific families (notably the BZR1/BES1 brassinosteroid-signaling transcription factors and plant beta-amylases) and at scattered sites in multipass membrane glycotransferases. | 5.45 | 3 |
| #7151 | N-terminal amphipathic helix start | N-terminal amphipathic alpha-helix initiation (the first helix and its N-cap/helix-start segment), marking the transition from a flexible N-terminus into the first stable helical element; a generic structural motif seen across diverse proteins and taxa, occasionally recurring at the starts of internal helices. | 5.24 | 9 |
| #15815 | Basic N-terminal targeting patch | Short, basic/polar N‑terminal leader/transit segment immediately after the initiator methionine (positions ~3–6) — i.e., the positively charged/polar start of signal peptides and organelle transit peptides, and more generally low‑acidic, disordered N‑terminal patches (including occasional cysteine‑rich starts) used for targeting, export, rRNA binding, or membrane topology cues | 4.46 | 3 |
| #1015 | Terminal amphipathic alpha-helix | Short terminal alpha-helical segments—most commonly the very N-terminal helix immediately following signal/transit peptides or the start methionine, and occasionally a short C‑terminal helix—typically the first helix of a folded domain or mature chain; these helices are often amphipathic and enriched in polar/charged residues | 4.39 | 21 |
| #5114 | Short N-terminal targeting arm | N-terminal segments (typically the first ~10 residues) across a wide range of bacterial, viral, and eukaryotic proteins. These are often signal/targeting/assembly arms, including RNA/DNA-binding tails, secretion/chaperone-binding regions, and assembly linkers. | 4.26 | 11 |
| #694 | NAELE-like N-terminal acidic patch | Short charged sequence patches with the motif "N-A-E-L-E" or related acidic/polar runs (often containing N, E, D, Q residues), commonly at the N-terminal portion of small bacterial regulatory and metalloenzyme proteins, including positions that are part of ordered helices, strands, and active-site loops. | 4.02 | 11 |
| #9497 | CLE C-termini and TM helix-ends | A heterogeneous, sparse residue-level feature that fires most strongly in two distinct contexts: (1) short disordered C-terminal extensions of small secreted peptide precursors, particularly CLE/CLAVATA3-family signaling peptides, and (2) single residues within transmembrane helices of small membrane regulators. | 3.96 | 3 |
| #10515 | Alpha/beta core helical packing | Alpha-helical packing segments of well-folded alpha/beta enzyme cores—especially the helical layers of (beta/alpha)8 TIM-barrels common in carbohydrate-active enzymes—largely excluding catalytic or ligand-binding sites. | 3.52 | 2 |
| #14233 | Helix N-cap/linker coil motifs | Short coil/turn helix-boundary motifs—especially positions immediately upstream of helix starts (i−1/i−2) and intra-/inter-helix linker loops—enriched in small/polar and Pro/Gly; strongest and periodic in ARM repeats but not ARM-specific. | 3.50 | 2 |
| #12647 | Helix caps and interhelical linkers | Residues at alpha-helix boundaries and the short loops/turns that link adjacent helices (helix–coil transition and helix-capping positions), i.e., N-/C-caps and interhelical linkers in helix–loop–helix segments and helical repeat motifs | 3.40 | 3 |
| #14922 | Coiled-coil heptad core detector | Heptad-repeat coiled-coil core detector: the feature marks one hydrophobic register (a or d positions) across alpha-helical coiled-coils that mediate oligomerization/dimerization, spanning long chemotaxis-receptor transducer stalks, SNARE coiled-coil motifs, and the dimerization helices of bHLH transcription factors. | 3.33 | 2 |
| #10341 | Boundary and processing residues | A short linear boundary/processing microfeature: residues that mark solvent-exposed boundaries of structural/functional units—helix/coil or coil/strand linkers, helix termini, and peptide/domain edges—including proteolytic maturation junctions; generally outside buried cores and transmembrane segments. | 3.32 | 2 |
| #10429 | Core helix-start activations | Recurrent core-region activation in soluble enzymes, with peaks at helix-start/helix-internal positions and immediately preceding loops; activations occur near but do not overlap catalytic or metal-binding sites | 3.28 | 2 |
| #8355 | Solvent-exposed helical patches | Short, solvent-exposed segments of well-ordered alpha helices—especially coil-to-helix N-cap regions and adjacent helical turns—forming generic helical surface patches used in coiled-coils, alpha-solenoids and helical bundles; not a catalytic motif but sometimes overlapping partner/ligand interfaces. | 3.19 | 2 |
| #2363 | Charged alpha-helical tracts | Polar/charged alpha-helical tracts (often low-complexity): E/D/K/R/S/T/N/Q-rich, low-aromatic segments occurring both in intrinsically disordered regions and as solvent-exposed helices within folded domains; these amphipathic/coiled-coil–like helices mediate oligomerization, nucleic-acid/protein binding, and assembly, especially in viral proteins. | 3.11 | 4 |
| #7265 | N-terminal initiator Met recognition | Recognition of the absolute protein N-terminus—specifically the initiator methionine (M1; often N-formylmethionine in bacteria/mitochondria) and the immediate +1 residue that becomes the mature N-terminus upon N-terminal methionine excision | 3.10 | 2 |
| #3299 | N-terminal targeting/pre-domain regions | Generic N-terminal leader/targeting and pre-domain segments: the model fires on the beginning-of-chain regions that encode export/targeting information (signal peptides; mitochondrial/chloroplast transit peptides) and on low-complexity/basic N-terminal tails or early amphipathic helices that precede the first structured/catalytic core; it can also extend into or occasionally recognize long internal helices that share the same physico-chemical profile. | 3.09 | 12 |
| #16313 | Catalytic-domain N-terminus motif | Short N-terminal segments at the start of the first catalytic domain, often coinciding with the first β-strand and active-site/substrate-binding residues, marking the beginning of the mature/folded core rather than a generic basic patch. | 2.81 | 6 |
| #5232 | Short amphipathic helices | Short amphipathic alpha-helical segments that mediate assembly, nucleic-acid/protein binding, or membrane association; common in intrinsically disordered regions or flexible linkers, but also present as coiled-coils or small helix-bundles within otherwise structured proteins; occasionally overlap or flank transmembrane helices. Enriched in mixed charged and hydrophobic residues. | 2.79 | 2 |
| #16250 | N-terminal first-helix motif | Onset of an N‑terminal alpha helix (N‑cap and first helical turn), typically marking the first helix of a helical hairpin/repeat unit (e.g., HTH/HEAT/EF‑hand/HhH) or an amphipathic transit helix, i.e., a generic structural “first-helix” motif rather than a specific function | 2.73 | 3 |
| #1677 | β→α junction hinge residues | Structured loop/turn residues at secondary‑structure junctions—especially β→α connectors and β‑turns—often Gly/Ser/Pro and acting as conserved hinge points that frequently flank (or abut) active or ligand‑binding sites across diverse enzymes and RNA/RNA‑binding proteins | 2.70 | 2 |
| #8732 | Mur ligase C-terminal subdomain | A mid/C-terminal domain feature of bacterial carboxylate-amine ligases of peptidoglycan biosynthesis (Mur synthetases: MurE/MurF-type UDP-N-acetylmuramoyl-peptide ligases and D-Ala–D-Ala-adding enzymes), extending to other nucleotide-using transferases (e.g., tRNA(Ile)-lysidine synthase, lipid A 4′-kinase); in some unrelated acyltransferases the feature collapses to the catalytic base residue. | 2.66 | 2 |
| #5406 | pfkB beta1–beta2 phosphate-binding loop | Phosphate/substrate-contacting loop at the front of the ribokinase‑like (pfkB) carbohydrate kinase fold (β1–β2 region that helps bind the sugar/phosphate group), with occasional weak hits to analogous nucleotide/AMP‑binding loops in other nucleotide‑handling proteins | 2.62 | 15 |
| #9830 | SAM-dependent MTase core helix | A structural alpha-helix within SAM-dependent methyltransferase catalytic domains—well-ordered helical scaffold elements flanking the central catalytic core that brace the SAM/substrate pocket; the feature prefers hydrophobic/basic residues in these helices and generalizes across diverse O-, N-, and C-methyltransferases (with occasional spillover to enzymes with similar helical scaffolds). | 2.62 | 2 |
| #2763 | N-terminal leaders and scaffolds | N-terminal segments at the start of proteins (~first 10-45 residues), covering a mix of cleavable targeting leaders (Sec/Tat signal peptides; chloroplast/thylakoid transit peptides) and noncleaved N-terminal regions that mediate cofactor binding, membrane association, or macromolecular assembly | 2.59 | 11 |
| #15598 | Aromatic and Gly/Pro phosphate-binding loops | Aromatic- and Gly/Pro-rich donor/ligand-binding loops that form nucleotide- or phosphate-bearing donor binding pockets of NDP-sugar–dependent glycosyltransferases (notably sialyltransferases and cell‑envelope polysaccharide assembly enzymes) and chemically analogous sites in enzymes that bind ribose- or phosphate-bearing ligands (nucleoside-processing enzymes, RNA nucleases, sugar kinases, and PEP-dependent pyruvyltransferases) | 2.57 | 14 |
Shared features by |Δ| activation — 1435 total (prevalence ≥ 2)
| Feature | Label | Description | Δ activation | Iso act. | Canon act. | Iso prev. | Canon prev. |
|---|---|---|---|---|---|---|---|
| #118 | N-terminal helix-start motif | A short N-terminal α-helix start/early-helix motif, with peaks landing on the first ordered α-helix near the N-terminus of α/β catalytic domains. The local sequence context tends to be hydrophobic/aromatic with a recurring Phe-Ser-(Glu/Asp) pattern flanked by basic residues, rather than a Pro/Gly-rich linker. | -3.34 | 4.87 | 8.21 | 9 | 15 |
| #16150 | N-terminal leader and secondary structure | N-terminal leader segments and the immediate start of the first structured element (β-strand/α-helix) at protein starts (and occasionally at internal domain starts); in eukaryotic precursors this region frequently overlaps organellar transit peptides. | -3.12 | 4.37 | 7.50 | 9 | 39 |
| #10181 | N-terminal amphipathic leader helix | Generic N-terminal amphipathic alpha-helix (“leader/N-helix”) with mixed hydrophobic and polar residues, often centered on a conserved His-containing motif, preceding the catalytic domain and not tied to catalytic sites; occasionally the same amphipathic helical patch appears slightly downstream (e.g., within transit peptides) or internally/C‑terminally | -2.21 | 3.18 | 5.39 | 20 | 38 |
| #3983 | Short conserved binding-site motifs | A feature that activates on short, conserved sequence motifs found in specific enzyme families, often co-located near cofactor/substrate-binding regions and at or adjacent to short structured elements (helix starts, strands, or helix–helix loops). | -2.07 | 1.97 | 4.04 | 2 | 10 |
| #12004 | N-terminal Pro/His helical motifs | Short N-terminal sequence motifs in metabolic enzymes, characterized by Pro- and His-containing patches embedded in early α-helical segments (e.g. S-P-x-P-Y/F-H in aspartyl aminopeptidases; G-H-P-D in S-adenosylmethionine synthases) | -1.86 | 4.78 | 6.64 | 6 | 10 |
| #13449 | Membrane-biased alpha-helix detector | Generic alpha-helix detector with strongest preference for long hydrophobic helices that associate with membranes (transmembrane segments and signal peptides), but also activating on extended coiled-coils and internal alpha-helices in soluble proteins | -1.47 | 7.37 | 8.84 | 15 | 22 |
| #12045 | Nucleotide phosphate-binding subdomain | A feature that marks a conserved internal region of the adenylation domain in AMP-forming acyl-CoA synthetases of the ANL superfamily, and may extend to analogous phosphate-coordinating subdomains in other α/β nucleotide-handling enzymes (e.g., Walker A P-loop NTPases, Rossmann-fold NAD(P)/SAM-binding enzymes, enolase-superfamily/metal-dependent phosphatases). | -1.41 | 2.09 | 3.50 | 5 | 21 |
| #12273 | Noncatalytic regulatory appendages | Non-catalytic accessory regions outside enzyme or core folds—most commonly long N‑terminal regulatory tails and membrane‑proximal stems (including signal‑anchor TMs), but also internal helical scaffolds—enriched for low‑complexity, Ser/Thr- and acidic‑rich sequence and short linear motifs (e.g., phosphosites, CxxC). These segments mediate regulation, localization, or complex assembly and are consistently avoided at catalytic/metal‑binding active‑site residues. | -1.40 | 4.96 | 6.36 | 35 | 54 |
| #2519 | Diffuse low-amplitude sequence-wide activation | Broadly distributed, low-amplitude feature that fires diffusely across many proteins, with frequent activation on polar residues (Thr, Ser) but also on charged and hydrophobic residues throughout both structured domains and disordered regions. | -1.34 | 2.47 | 3.81 | 7 | 8 |
| #9215 | Complex I NuoD core motif | Family-specific feature for the conserved N-terminal core of the Complex I 49 kDa / NuoD-type NADH:quinone oxidoreductase subunit (and the related NDUFAF6 assembly factor), marking conserved residues around the YVSMM…(N/C/Q)EHxY motif and a downstream F-E-E-R-E-K-L block. | +1.32 | 7.38 | 6.05 | 9 | 7 |
| #2234 | Eukaryotic N-terminal targeting signals | Eukaryotic N-terminal low-complexity, Ser/Thr- and Lys/Arg-rich leader segments that predominantly function as organelle-targeting presequences (especially chloroplast transit peptides), with spillover to mitochondrial targeting peptides, N-terminal peroxisomal PTS2 signals, and secretory signal peptides; the feature also activates on non-targeting disordered/basic N-termini in cytosolic proteins. | -1.32 | 2.26 | 3.58 | 2 | 12 |
| #7043 | Exposed helical scaffold surfaces | Exposed alpha-helical structural elements—particularly well-ordered helices and their N/C-capping positions—serving as generic interaction/scaffold surfaces (often charged), rather than family-specific catalytic motifs | -1.29 | 3.21 | 4.50 | 6 | 11 |
| #11395 | Spire KIND/WH2 with charged LCRs | Conserved motifs within the KIND domain and flanking the WH2 actin-binding motifs of Spire family actin nucleators, together with low-complexity, intrinsically disordered regions enriched in charged/polar residues (E/D/S/T/K/R) in other proteins; occasionally shows weaker signal within or flanking helical segments (e.g., transmembrane or coiled-coil boundaries). | -1.29 | 2.27 | 3.56 | 5 | 6 |
| #6384 | Widespread activation in folded proteins | Proteins showing broad, diffuse activation across large fractions of their sequence, with peaks frequently occurring in folded regions of single-domain or multi-domain enzymes and structural proteins. | +1.24 | 4.34 | 3.10 | 17 | 14 |
| #8494 | Alpha-helical hydrophobic packing | Generic structural signal of hydrophobic/aromatic residues within well-ordered alpha-helices of folded domains (helical packing/core or helix–helix interface positions), largely independent of specific catalytic sites or functions. | -1.24 | 4.17 | 5.41 | 10 | 15 |
| #11788 | Bacterial enzyme N-termini | Activates on N-terminal regions of bacterial/archaeal enzyme subunits, including both non-cleavable signal-anchor transmembrane helices of membrane-anchored redox subunits and N-terminal segments of soluble oxygenase/hydroxylase and cyclohydrolase subunits. | -1.10 | 5.64 | 6.74 | 20 | 42 |
| #3703 | Organelle mature domain activator | Mature, structured domains of organelle-targeted precursor proteins (predominantly plant chloroplast and mitochondrial), with strong preference for conserved functional cores (DNA/RNA‑binding motifs, catalytic folds, and transmembrane helices) and avoidance of N‑terminal transit peptides and extended low‑complexity tails. | +1.08 | 4.71 | 3.63 | 284 | 244 |
| #7486 | Generic alpha-helical scaffold signal | Generic alpha-helical scaffold signal: the feature marks short internal stretches of well-ordered alpha helices and adjacent helix–loop junctions across diverse proteins, especially in all‑alpha/alpha‑repeat domains (e.g., cyclin box, PUF repeats) and also in transmembrane helices; it reflects structural packing/architecture rather than catalytic or ligand-binding motifs. | +1.07 | 7.76 | 6.69 | 13 | 12 |
| #9297 | Soluble amphipathic helical interfaces | Amphipathic, non‑membrane alpha‑helical segments in soluble helical‑bundle scaffolds, often forming or bordering protein–protein or small‑molecule interaction surfaces (e.g., four‑helix bundles, helical adaptor/repeat domains, coiled‑coil/HAMP‑like regions) | -1.02 | 4.46 | 5.48 | 4 | 7 |
| #14234 | Ordered cores and transmembrane helices | Generic preference for ordered chain regions of folded proteins, with particularly strong responses in hydrophobic α-helices that span membranes; avoids signal peptides and low-confidence N-terminal precursor regions. | -1.02 | 5.38 | 6.40 | 14 | 17 |
| #9363 | Extreme N-terminal tail activation | N-terminal segments preceding the first structured catalytic domain—often disordered or coil-like and frequently enriched in hydrophobic/proline residues, though basic/low-complexity patches also activate. These regions correspond to leader/tail segments (e.g., cytosolic tails before a transmembrane helix, pre/pro-peptides, transit peptides, or conserved N-terminal extensions of catalytic chains). | -0.96 | 3.08 | 4.04 | 14 | 36 |
| #3108 | Secondary-structure boundary loops | Short secondary-structure boundary segments—loops/turns at the start of helices or edge β-strands and their immediately adjacent residues—often used as flexible recognition/regulatory sites; these regions are enriched in charged/polar residues (frequent Ser/Thr and Lys/Arg/Asp/Glu) with common Gly/Pro and can include modification or disulfide-forming positions. | -0.94 | 1.85 | 2.79 | 2 | 11 |
| #7572 | Conserved catalytic helix motif | A conserved internal sequence/structural motif within enzyme catalytic domains, prominently exemplified by the "DRL(V/I)G(x)YEE" segment of the glutamate mutase epsilon subunit, where activation peaks on a short hydrophobic-aromatic stretch embedded in an α-helix close to cofactor/substrate binding residues. | -0.90 | 2.14 | 3.04 | 3 | 22 |
| #11860 | Peripheral domain boundary linkers | Short segments at domain boundaries and adjacent loops — often Pro-rich or acidic linker-like stretches, sometimes containing clustered Lys/Arg — that act as flexible linkers or peripheral, solvent-exposed elements rather than core catalytic motifs | -0.90 | 2.08 | 2.98 | 9 | 9 |
| #1156 | Membrane-interfacial hydrophobic stretches | Extended hydrophobic/aromatic-rich secondary-structure runs—typically membrane-interfacial segments (transmembrane helices or outer-membrane beta-barrel strands) together with their immediate flanking loops, and, in soluble proteins, analogous hydrophobic helical/strand blocks at domain starts/ends or linkers (often following positive-inside/aromatic-boundary patterns). | -0.89 | 5.41 | 6.29 | 44 | 66 |
| #11911 | Short Lys/Arg-rich patches | Short sequence patches—often Lys/Arg-enriched and sometimes mixed with acidic residues—typically 8–25 residues long, frequently occurring in disordered N-terminal segments but also within ordered regions of diverse proteins, often associated with RNA/ribosome-contact surfaces or assembly interfaces. | -0.88 | 2.85 | 3.72 | 17 | 32 |
| #7534 | Alpha-helical interaction modules | Alpha-helical interaction elements in eukaryotic regulators—recognition helices and small helical bundles (e.g., homeobox/POU helices, bromodomains, OVATE), coiled-coils, and amphipathic helices that form macromolecular binding surfaces for DNA, chromatin marks, and protein partners; enriched at hydrophobic L/I/V/F positions with interspersed S/T/E/D | +0.85 | 4.24 | 3.39 | 5 | 3 |
| #4764 | Unknown generic feature | Unknown generic feature | +8.09 | 10.05 | 1.97 | 3 | 2 |
| #14534 | Unknown generic feature | Unknown generic feature | -5.95 | 10.51 | 16.45 | 211 | 243 |
| #9005 | Unknown generic feature | Unknown generic feature | -1.52 | 12.16 | 13.68 | 165 | 200 |
Part 2 · Differential coordinates
Features firing on just the canonical-lost (truncated) residues.
Unique-region features — 146 distinct (prevalence ≥ 2)
| Feature | Label | Description | Activation | Prevalence |
|---|---|---|---|---|
| #1108 | N-terminal amphipathic interaction helices | Long amphipathic alpha-helical segments, typically at the N-terminus, that serve as interaction/capping elements in soluble proteins (e.g., coiled-coil/connector helices in complexes, DNA-binding HTH helices, and helical lids adjacent to active sites), enriched in charged, helix-forming residues | 10.62 | 19 |
| #4485 | Hydrophobic alpha-helical segments | Hydrophobic alpha-helical segments in soluble globular proteins, prominently a conserved helix near the active site of glycoside hydrolase family 27 alpha-galactosidases. | 9.73 | 16 |
| #13449 | Membrane-biased alpha-helix detector | Generic alpha-helix detector with strongest preference for long hydrophobic helices that associate with membranes (transmembrane segments and signal peptides), but also activating on extended coiled-coils and internal alpha-helices in soluble proteins | 8.84 | 6 |
| #118 | N-terminal helix-start motif | A short N-terminal α-helix start/early-helix motif, with peaks landing on the first ordered α-helix near the N-terminus of α/β catalytic domains. The local sequence context tends to be hydrophobic/aromatic with a recurring Phe-Ser-(Glu/Asp) pattern flanked by basic residues, rather than a Pro/Gly-rich linker. | 8.21 | 6 |
| #12048 | Generic secondary-structure context marker | A near-ubiquitous, low-amplitude feature marking generic local secondary-structure context—residues within α-helices, β-strands, and the connecting loops—with a frequent emphasis on helix–coil junctions and domain/linker regions, independent of residue type, function, or taxonomy. | 7.60 | 2 |
| #14355 | Generic helical order signal | A generic structural signal for ordered alpha-helices—activating on well-packed helical elements in both soluble domains (e.g., SEC7) and transmembrane segments, as well as extended coiled-coil regions; not tied to a specific sequence motif or function. | 7.59 | 2 |
| #16150 | N-terminal leader and secondary structure | N-terminal leader segments and the immediate start of the first structured element (β-strand/α-helix) at protein starts (and occasionally at internal domain starts); in eukaryotic precursors this region frequently overlaps organellar transit peptides. | 7.50 | 19 |
| #6943 | Ordered helical segment marker | Residue-level signal for well-ordered alpha‑helical segments—covering coiled‑coils, soluble helices and, in some cases, transmembrane helices—rather than a specific sequence motif; the feature tends to mark stable helical cores and helix boundary/interface positions within structured regions while avoiding disordered tails. | 7.45 | 3 |
| #12684 | Alpha-helix boundary preference | Alpha-helical context: residues within or immediately adjacent to alpha-helices, with a bias toward membrane-proximal helices (first transmembrane segments and short juxtamembrane helices) and short N‑terminal/domain-start helices; also responsive to long coiled‑coil helices in soluble proteins. | 7.30 | 3 |
| #5850 | Basic amphipathic helical segments | Amphipathic, basic/aliphatic-enriched helical segments—covering coiled‑coil/dimerization helices and post-cleavage mitochondrial-matrix loops adjacent to inner-membrane anchors—used for oligomerization, scaffolding, and membrane-protein assembly across diverse proteins. | 7.21 | 3 |
| #2530 | LTV1/MPP10 motifs, TruD helix | Sequence-specific motif feature active in ribosome/snoRNP biogenesis factors and TruD-family pseudouridine synthases. In LTV1 homologs the feature recognizes a conserved internal "SSVxRRNEQL"-like motif, and in MPP10 homologs it recognizes a conserved "P(A/V)PVITEE" motif. In TruD/PUS7-family proteins it activates along an internal alpha-helix within the TRUD catalytic domain. | 6.99 | 2 |
| #7565 | Hydrophobic helices and signals | Generic, low-specificity signal for short hydrophobic/alpha-helical stretches with a mild N-terminal bias, encompassing signal/transit peptides, single-pass transmembrane anchors, and coiled-coil helices; also yields weak single-residue responses to hydrophobic/aromatic positions within structured loops and peptide-hormone segments. | 6.86 | 2 |
| #11788 | Bacterial enzyme N-termini | Activates on N-terminal regions of bacterial/archaeal enzyme subunits, including both non-cleavable signal-anchor transmembrane helices of membrane-anchored redox subunits and N-terminal segments of soluble oxygenase/hydroxylase and cyclohydrolase subunits. | 6.74 | 19 |
| #12004 | N-terminal Pro/His helical motifs | Short N-terminal sequence motifs in metabolic enzymes, characterized by Pro- and His-containing patches embedded in early α-helical segments (e.g. S-P-x-P-Y/F-H in aspartyl aminopeptidases; G-H-P-D in S-adenosylmethionine synthases) | 6.64 | 4 |
| #14234 | Ordered cores and transmembrane helices | Generic preference for ordered chain regions of folded proteins, with particularly strong responses in hydrophobic α-helices that span membranes; avoids signal peptides and low-confidence N-terminal precursor regions. | 6.40 | 2 |
| #12273 | Noncatalytic regulatory appendages | Non-catalytic accessory regions outside enzyme or core folds—most commonly long N‑terminal regulatory tails and membrane‑proximal stems (including signal‑anchor TMs), but also internal helical scaffolds—enriched for low‑complexity, Ser/Thr- and acidic‑rich sequence and short linear motifs (e.g., phosphosites, CxxC). These segments mediate regulation, localization, or complex assembly and are consistently avoided at catalytic/metal‑binding active‑site residues. | 6.36 | 19 |
| #1156 | Membrane-interfacial hydrophobic stretches | Extended hydrophobic/aromatic-rich secondary-structure runs—typically membrane-interfacial segments (transmembrane helices or outer-membrane beta-barrel strands) together with their immediate flanking loops, and, in soluble proteins, analogous hydrophobic helical/strand blocks at domain starts/ends or linkers (often following positive-inside/aromatic-boundary patterns). | 6.29 | 19 |
| #4663 | Helical hydrophobic-aromatic binding motif | Conserved hydrophobic-aromatic motifs embedded in functional protein-protein and cofactor-binding sites, including the [4Fe-4S] cluster-binding region of archaeal DNA primase large subunit (PriL) and the CDK-binding "Speedy/Ringo box" of Speedy proteins | 6.21 | 13 |
| #8003 | Polar low-complexity kinase IDRs | Broad, sequence-wide activation across eukaryotic lipid-metabolism kinases and NAD/NADH kinases, with the strongest peaks concentrated in disordered, low-complexity/polar-rich segments (often Ser/Thr/Pro/Gly-rich). The feature fires throughout the protein but reaches its maxima in compositionally biased, intrinsically disordered regions. | 5.77 | 19 |
| #8494 | Alpha-helical hydrophobic packing | Generic structural signal of hydrophobic/aromatic residues within well-ordered alpha-helices of folded domains (helical packing/core or helix–helix interface positions), largely independent of specific catalytic sites or functions. | 5.41 | 4 |
| #10181 | N-terminal amphipathic leader helix | Generic N-terminal amphipathic alpha-helix (“leader/N-helix”) with mixed hydrophobic and polar residues, often centered on a conserved His-containing motif, preceding the catalytic domain and not tied to catalytic sites; occasionally the same amphipathic helical patch appears slightly downstream (e.g., within transit peptides) or internally/C‑terminally | 5.39 | 14 |
| #625 | Phosphate-handling catalytic cores | Catalytic cores of large soluble enzymes that bind and process phosphate-bearing ligands (nucleic acids, nucleotides, or diphosphate cofactors), with emphasis on acidic/glycine-rich loops and adjacent helices/strands that scaffold and coordinate catalysis. | 5.34 | 4 |
| #5707 | INRE-like short charged blocks | Short internal sequence blocks with a recurring (I/L)-N-R-E-(P/I)-F–like motif and surrounding charged residues, found in cobalamin-dependent isomerases and in other diverse bacterial/archaeal proteins | 5.19 | 14 |
| #6016 | Helix-biased internal methionine detector | Detector for methionine residues, firing on internal Met across diverse proteins with somewhat enhanced response when Met occurs in helical or low-complexity contexts; occasional hits at the initiator Met when embedded in a locally Met- or hydrophobic-rich N-terminus; weak cross-reactivity to other bulky hydrophobics (notably tryptophan). | 5.04 | 2 |
| #14895 | Unknown generic feature | Unknown generic feature | 19.06 | 19 |
| #9214 | Unknown generic feature | Unknown generic feature | 18.92 | 19 |
| #1803 | Unknown generic feature | Unknown generic feature | 16.61 | 19 |
| #14534 | Unknown generic feature | Unknown generic feature | 16.45 | 19 |
| #9194 | Unknown generic feature | Unknown generic feature | 13.34 | 19 |
| #9005 | Unknown generic feature | Unknown generic feature | 10.75 | 15 |
Top-K sparse-autoencoder activations on the ESM-C residual stream. Activation is a feature's peak value over its region; Prevalence is the number of residues it fires on; Δ activation is isoform − canonical. Only the top 30 features per category are saved; generic / "unknown" features are hidden until you expand a table. Read more about SAE features →
Clinical variants
Differential region — lost N-terminus (canonical-only)
| Pos (iso) | AA change | Consequence | Source | Clin. sig. | AF (gnomAD) | Impact | AlphaMissense | ESM-C ΔLLR | Link |
|---|---|---|---|---|---|---|---|---|---|
| — | P→R | intronic | gnomAD | — | 6.84e-07 | — | likely_benign (0.15) | -4.97 | chr12-123632407-G-C |
| — | P→A | intronic | gnomAD | — | 6.84e-07 | — | likely_benign (0.10) | -4.84 | chr12-123632408-G-C |
| — | — | intronic | gnomAD | — | 6.84e-07 | damaging | — | — | chr12-123632411-CTTCT-C |
| — | E→A | intronic | gnomAD | — | 6.84e-07 | — | likely_benign (0.08) | -3.62 | chr12-123632413-T-G |
| — | K→K | intronic | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123632415-T-C |
| — | K→R | intronic | gnomAD | — | 6.84e-07 | — | likely_benign (0.07) | 0.66 | chr12-123632416-T-C |
| — | — | intronic | gnomAD | — | 2.05e-06 | damaging | — | — | chr12-123632418-C-CA |
| — | M→I | intronic | gnomAD | — | 1.37e-06 | — | likely_benign (0.28) | -1.50 | chr12-123632418-C-T |
| — | Q→H | intronic | gnomAD | — | 6.57e-05 | — | likely_benign (0.28) | -4.98 | chr12-123632421-C-G |
| — | Q→Q | intronic | gnomAD | — | 5.47e-06 | — | — | 0.00 | chr12-123632421-C-T |
| — | S→F | intronic | gnomAD | — | 1.37e-06 | — | likely_benign (0.13) | -3.95 | chr12-123632425-G-A |
| — | S→C | intronic | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | -3.64 | chr12-123632425-G-C |
| — | — | intronic | gnomAD | — | 6.84e-07 | damaging | — | — | chr12-123632427-CTT-C |
| — | — | intronic | gnomAD | — | 6.84e-07 | damaging | — | — | chr12-123632427-CTTAAAGTA-C |
| — | K→E | intronic | gnomAD | — | 4.79e-06 | — | likely_benign (0.10) | -3.16 | chr12-123632429-T-C |
| — | — | intronic | gnomAD | — | 6.85e-07 | damaging | — | — | chr12-123632429-T-TA |
| — | F→S | intronic | gnomAD | — | 6.16e-06 | damaging | likely_pathogenic (0.97) | -9.11 | chr12-123632431-A-G |
| — | F→I | intronic | gnomAD | — | 6.85e-07 | damaging | likely_pathogenic (0.87) | -8.79 | chr12-123632432-A-T |
| — | — | intronic | gnomAD | — | 1.37e-06 | damaging | — | — | chr12-123632433-GTA-G |
| — | I→T | intronic | gnomAD | — | 1.37e-06 | — | likely_benign (0.06) | -2.15 | chr12-123632440-A-G |
| — | I→V | intronic | gnomAD | — | 1.37e-06 | — | likely_benign (0.07) | 1.15 | chr12-123632441-T-C |
| — | E→E | intronic | gnomAD | — | 1.03e-05 | — | — | 0.00 | chr12-123632445-C-T |
| — | E→K | intronic | gnomAD | — | 1.23e-05 | — | likely_benign (0.17) | -4.77 | chr12-123633545-C-T |
| — | K→K | intronic | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123633546-C-T |
| — | — | intronic | gnomAD | — | 6.84e-07 | — | — | — | chr12-123633548-TGTC-T |
| — | D→D | intronic | gnomAD | — | 1.78e-05 | — | — | 0.00 | chr12-123633549-G-A |
| — | D→Y | intronic | gnomAD | — | 1.19e-04 | — | likely_benign (0.18) | -5.67 | chr12-123633551-C-A |
| — | D→H | intronic | gnomAD | — | 1.16e-05 | — | likely_benign (0.15) | -3.36 | chr12-123633551-C-G |
| — | D→N | intronic | gnomAD | — | 6.85e-07 | — | likely_benign (0.08) | -1.03 | chr12-123633551-C-T |
| — | D→H | intronic | gnomAD | — | 6.85e-07 | — | likely_benign (0.22) | -5.42 | chr12-123633554-C-G |
| — | D→N | intronic | gnomAD | — | 6.85e-07 | — | likely_benign (0.08) | -2.21 | chr12-123633554-C-T |
| — | M→V | intronic | gnomAD | — | 6.85e-07 | — | — | -6.96 | chr12-123633557-T-C |
| — | D→Y | intronic | ClinVar | Uncertain significance | — | — | likely_benign (0.18) | -5.67 | ClinVar:813657 |
| — | M→I | intronic | ClinVar | Uncertain significance | — | — | likely_benign (0.28) | -1.50 | ClinVar:1345195 |
| — | E→K | intronic | ClinVar | Uncertain significance | — | — | likely_benign (0.17) | -4.77 | ClinVar:2176384 |
| — | Q→H | intronic | ClinVar | Uncertain significance | — | — | likely_benign (0.28) | -4.98 | ClinVar:2185148 |
| — | L→S | intronic | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.77) | -4.98 | ClinVar:2296169 |
| — | — | intronic | ClinVar | Pathogenic | — | damaging | — | — | ClinVar:2858770 |
| — | — | intronic | ClinVar | Pathogenic | — | damaging | — | — | ClinVar:2874636 |
| — | E→E | intronic | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2877544 |
| — | — | intronic | ClinVar | Pathogenic | — | damaging | — | — | ClinVar:2962147 |
| — | Y→Y | intronic | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3692403 |
| — | E→K | intronic | COSMIC | — | — | — | likely_benign (0.09) | -3.59 | COSV99967654 |
| — | Q→R | intronic | COSMIC | — | — | — | likely_benign (0.12) | -4.32 | COSV99967622 |
| — | E→* | intronic | COSMIC | — | — | damaging | — | — | COSV106331808 |
45 variants in the differential region.
Shared canonical core — sequence common to canonical and isoform; AlphaMissense applies here
| Pos (iso) | AA change | Consequence | Source | Clin. sig. | AF (gnomAD) | Impact | AlphaMissense | ESM-C ΔLLR | Link |
|---|---|---|---|---|---|---|---|---|---|
| 0 | M→V | missense_variant | gnomAD | — | 4.10e-06 | — | likely_benign (0.08) | -1.69 | chr12-123632402-T-C |
| 0 | M→T | missense_variant | COSMIC | — | — | — | likely_benign (0.14) | -4.32 | COSV57459585 |
| 1 | A→A | synonymous_variant | gnomAD | — | 6.23e-05 | — | — | 0.00 | chr12-123632397-G-A |
| 1 | A→V | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.70) | -5.98 | chr12-123632398-G-A |
| 1 | A→P | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.29) | -5.80 | chr12-123632399-C-G |
| 1 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1621049 |
| 2 | S→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123632395-G-C |
| 2 | S→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2767181 |
| 2 | S→S | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV57459031 |
| 3 | A→A | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123632391-T-C |
| 5 | A→S | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.30) | -5.36 | chr12-123632387-C-A |
| 6 | A→A | synonymous_variant | gnomAD | — | 4.79e-06 | — | — | 0.00 | chr12-123632382-G-A |
| 6 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2961048 |
| 7 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123632379-G-A |
| 7 | I→M | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.31) | -6.30 | chr12-123632379-G-C |
| 7 | I→N | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.94) | -8.61 | chr12-123632380-A-T |
| 8 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123632376-C-A |
| 8 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123632376-C-G |
| 8 | R→Q | missense_variant | gnomAD | — | 2.53e-05 | — | likely_benign (0.10) | -4.94 | chr12-123632377-C-T |
| 8 | R→W | missense_variant | gnomAD | — | 5.47e-05 | — | likely_benign (0.28) | -7.19 | chr12-123632378-G-A |
| 8 | R→W | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.28) | -7.19 | ClinVar:1386755 |
| 8 | R→Q | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.10) | -4.94 | ClinVar:1915443 |
| 8 | R→W | missense_variant | COSMIC | — | — | — | likely_benign (0.28) | -7.19 | COSV57459867 |
| 9 | T→T | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123632373-C-A |
| 9 | T→T | synonymous_variant | gnomAD | — | 5.47e-06 | — | — | 0.00 | chr12-123632373-C-T |
| 9 | T→M | missense_variant | gnomAD | — | 5.47e-06 | damaging | ambiguous (0.40) | -7.62 | chr12-123632374-G-A |
| 9 | T→T | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2875935 |
| 9 | T→M | missense_variant | COSMIC | — | — | damaging | ambiguous (0.40) | -7.62 | COSV57459816 |
| 9 | T→S | missense_variant | COSMIC | — | — | — | likely_benign (0.23) | -3.75 | COSV57459822 |
| 13 | F→F | synonymous_variant | gnomAD | — | 6.85e-07 | — | — | 0.00 | chr12-123632361-G-A |
| 13 | F→F | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2998111 |
| 14 | L→F | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.75) | -6.32 | COSV57459800 |
| 15 | K→N | missense_variant | gnomAD | — | 6.86e-07 | — | ambiguous (0.45) | -5.51 | chr12-123632355-C-A |
| 15 | K→K | synonymous_variant | gnomAD | — | 2.06e-06 | — | — | 0.00 | chr12-123632355-C-T |
| 15 | K→K | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2832238 |
| 15 | K→N | missense_variant | COSMIC | — | — | — | ambiguous (0.45) | -5.51 | COSV99967567 |
| 16 | — | frameshift_variant | gnomAD | — | 6.86e-07 | LoF | — | — | chr12-123632353-CTCTT-C |
| 16 | R→T | missense_variant | COSMIC | — | — | — | likely_benign (0.14) | -6.80 | COSV57458514 |
| 17 | D→H | missense_variant | gnomAD | — | 6.88e-07 | damaging | likely_pathogenic (0.76) | -6.14 | chr12-123632351-C-G |
| 17 | D→H | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.76) | -6.14 | ClinVar:1976823 |
| 18 | K→E | missense_variant | gnomAD | — | 2.06e-06 | — | likely_benign (0.08) | -3.62 | chr12-123632348-T-C |
| 19 | G→E | missense_variant | gnomAD | — | 6.85e-07 | — | ambiguous (0.34) | -3.34 | chr12-123630533-C-T |
| 19 | G→G | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2826906 |
| 19 | G→R | missense_variant | ClinVar | — | — | damaging | likely_pathogenic (0.63) | -6.69 | ClinVar:4381679 |
| 20 | E→D | missense_variant | COSMIC | — | — | — | likely_benign (0.23) | -3.13 | COSV57458205 |
| 20 | — | mnv | COSMIC | — | — | — | — | — | COSV104564172 |
| 21 | T→A | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.87) | -7.31 | COSV108005029 |
| 22 | I→M | missense_variant | gnomAD | — | 6.85e-07 | — | likely_benign (0.18) | -3.83 | chr12-123630523-G-C |
| 22 | I→V | missense_variant | gnomAD | — | 6.85e-06 | — | likely_benign (0.11) | -3.40 | chr12-123630525-T-C |
| 22 | I→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.11) | -3.40 | ClinVar:1480504 |
| 23 | Q→R | missense_variant | gnomAD | — | 6.85e-07 | — | likely_benign (0.25) | -5.98 | chr12-123630521-T-C |
| 24 | G→D | missense_variant | ClinVar | Likely pathogenic | — | damaging | likely_pathogenic (0.76) | -4.81 | ClinVar:2443120 |
| 25 | L→L | synonymous_variant | gnomAD | — | 6.85e-07 | — | — | 0.00 | chr12-123630514-C-G |
| 26 | R→R | synonymous_variant | gnomAD | — | 4.11e-06 | — | — | 0.00 | chr12-123630513-T-G |
| 26 | R→R | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2719860 |
| 27 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630508-C-G |
| 27 | A→A | synonymous_variant | gnomAD | — | 3.42e-06 | — | — | 0.00 | chr12-123630508-C-T |
| 27 | A→V | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.13) | -0.89 | chr12-123630509-G-A |
| 27 | A→T | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.08) | -1.75 | chr12-123630510-C-T |
| 27 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2976088 |
| 27 | A→A | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV57460265 |
| 27 | A→V | missense_variant | COSMIC | — | — | — | likely_benign (0.13) | -0.89 | COSV99967503 |
| 28 | N→D | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.16) | -4.94 | chr12-123630507-T-C |
| 29 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630502-G-A |
| 29 | L→F | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.68) | -6.74 | COSV57458047 |
| 30 | T→T | synonymous_variant | gnomAD | — | 3.08e-05 | — | — | 0.00 | chr12-123630499-G-C |
| 30 | T→T | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:753274 |
| 32 | A→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.20) | -5.10 | chr12-123630495-C-T |
| 32 | A→V | missense_variant | COSMIC | — | — | — | likely_benign (0.29) | -4.69 | COSV99967521 |
| 33 | I→M | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -4.86 | chr12-123630490-T-C |
| 33 | I→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.08) | -3.81 | chr12-123630492-T-C |
| 34 | E→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.24) | -5.71 | ClinVar:4247691 |
| 35 | T→T | synonymous_variant | gnomAD | — | 4.10e-06 | — | — | 0.00 | chr12-123630484-G-C |
| 35 | T→S | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -3.18 | chr12-123630486-T-A |
| 35 | T→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | -3.04 | chr12-123630486-T-C |
| 35 | T→S | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.13) | -3.18 | ClinVar:1507295 |
| 36 | L→L | synonymous_variant | gnomAD | — | 5.47e-06 | — | — | 0.00 | chr12-123630481-C-G |
| 36 | L→P | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -9.79 | chr12-123630482-A-G |
| 36 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3003025 |
| 36 | L→M | missense_variant | COSMIC | — | — | — | likely_benign (0.23) | -5.07 | COSV99967509 |
| 37 | C→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:3639835 |
| 38 | G→G | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123630475-A-G |
| 39 | V→A | missense_variant | gnomAD | — | 5.66e-04 | — | likely_benign (0.13) | -3.56 | chr12-123630473-A-G |
| 39 | V→A | missense_variant | ClinVar | Benign/Likely benign | — | — | likely_benign (0.13) | -3.56 | ClinVar:883546 |
| 39 | V→A | missense_variant | COSMIC | — | — | — | likely_benign (0.13) | -3.56 | COSV57459432 |
| 40 | D→H | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.80) | -6.95 | chr12-123630471-C-G |
| 41 | S→F | missense_variant | gnomAD | — | 1.37e-06 | — | ambiguous (0.44) | -5.57 | chr12-123630467-G-A |
| 42 | S→F | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.79) | -7.59 | chr12-123630464-G-A |
| 43 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630460-C-T |
| 43 | V→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.68) | -5.61 | chr12-123630462-C-A |
| 44 | A→A | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123630457-T-G |
| 44 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1906785 |
| 45 | V→A | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.78) | -6.86 | chr12-123630455-A-G |
| 47 | S→S | synonymous_variant | gnomAD | — | 7.94e-05 | — | — | 0.00 | chr12-123630448-A-G |
| 47 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2977946 |
| 47 | S→F | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.98) | -9.37 | COSV57459760 |
| 47 | S→C | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.59) | -8.25 | COSV99967639 |
| 48 | G→G | synonymous_variant | gnomAD | — | 3.83e-05 | — | — | 0.00 | chr12-123630445-G-A |
| 48 | G→G | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630445-G-T |
| 48 | G→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.77) | -8.56 | chr12-123630446-C-A |
| 48 | G→S | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.40) | -6.71 | chr12-123630447-C-T |
| 48 | G→G | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2974054 |
| 49 | G→G | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630442-C-A |
| 49 | G→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.22) | -5.95 | chr12-123630443-C-G |
| 49 | G→R | missense_variant | gnomAD | — | 4.10e-06 | damaging | likely_pathogenic (0.97) | -7.48 | chr12-123630444-C-T |
| 49 | G→R | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.97) | -7.48 | ClinVar:3375980 |
| 52 | F→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -6.24 | chr12-123630433-G-T |
| 52 | F→F | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV57458307 |
| 54 | R→R | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123630427-G-A |
| 54 | R→H | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.57) | -6.30 | chr12-123630428-C-T |
| 54 | R→R | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2083276 |
| 55 | F→F | synonymous_variant | gnomAD | — | 1.03e-05 | — | — | 0.00 | chr12-123630424-G-A |
| 55 | F→F | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2978592 |
| 55 | F→L | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.99) | -7.00 | COSV57459047 |
| 56 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630421-G-A |
| 56 | I→I | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV57459564 |
| 56 | I→M | missense_variant | COSMIC | — | — | — | ambiguous (0.51) | -6.42 | COSV57458414 |
| 56 | — | inframe_deletion | COSMIC | — | — | — | — | — | COSV57460141 |
| 58 | L→V | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.46) | -6.86 | chr12-123630417-G-C |
| 58 | L→I | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.45) | -7.24 | chr12-123630417-G-T |
| 59 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630412-G-A |
| 59 | A→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | 3.34 | chr12-123630414-C-T |
| 59 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3701756 |
| 60 | S→T | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.12) | -3.84 | ClinVar:2124902 |
| 60 | S→S | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV57458728 |
| 60 | S→F | missense_variant | COSMIC | — | — | — | ambiguous (0.48) | -4.12 | COSV99967684 |
| 61 | L→L | synonymous_variant | gnomAD | — | 4.38e-05 | — | — | 0.00 | chr12-123630408-G-A |
| 61 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1638519 |
| 61 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2778378 |
| 62 | E→E | synonymous_variant | gnomAD | — | 6.16e-06 | — | — | 0.00 | chr12-123630403-T-C |
| 62 | E→Q | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.41) | -5.31 | chr12-123630405-C-G |
| 62 | E→E | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1938019 |
| 63 | Y→Y | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123630400-G-A |
| 63 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630402-A-AC |
| 64 | S→S | synonymous_variant | gnomAD | — | 1.30e-05 | — | — | 0.00 | chr12-123630397-G-A |
| 64 | S→C | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.16) | -6.30 | chr12-123630398-G-C |
| 64 | S→S | synonymous_variant | ClinVar | Uncertain significance | — | — | — | 0.00 | ClinVar:593688 |
| 64 | S→F | missense_variant | COSMIC | — | — | — | likely_benign (0.30) | -6.67 | COSV57459824 |
| 65 | D→E | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.28) | -2.87 | chr12-123630283-A-T |
| 65 | D→V | missense_variant | gnomAD | — | 1.37e-06 | damaging | ambiguous (0.48) | -8.19 | chr12-123630284-T-A |
| 66 | Y→Y | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630280-G-A |
| 66 | Y→S | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.35) | -1.47 | chr12-123630281-T-G |
| 66 | Y→Y | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2778868 |
| 66 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2828613 |
| 69 | C→R | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.91) | -6.12 | COSV57459610 |
| 70 | K→R | missense_variant | gnomAD | — | 4.10e-06 | — | likely_benign (0.10) | -3.44 | chr12-123630269-T-C |
| 70 | — | frameshift_variant | COSMIC | — | — | LoF | — | — | COSV104391797 |
| 71 | K→K | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123630265-C-T |
| 72 | I→M | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.11) | -2.85 | chr12-123630262-G-C |
| 72 | I→N | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.30) | -3.80 | chr12-123630263-A-T |
| 72 | I→V | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.09) | -0.03 | chr12-123630264-T-C |
| 73 | M→K | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.93) | -9.19 | COSV104564174 |
| 74 | I→T | missense_variant | gnomAD | — | 6.16e-06 | — | likely_benign (0.10) | -3.50 | chr12-123630257-A-G |
| 75 | E→D | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.14) | -0.03 | chr12-123630253-C-G |
| 75 | E→E | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630253-C-T |
| 75 | E→G | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.17) | -4.98 | chr12-123630254-T-C |
| 75 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123630255-C-CA |
| 75 | E→E | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:4807060 |
| 76 | R→Q | missense_variant | gnomAD | — | 4.10e-06 | damaging | likely_pathogenic (0.60) | -5.36 | chr12-123630251-C-T |
| 76 | R→W | missense_variant | gnomAD | — | 2.74e-06 | damaging | likely_pathogenic (0.87) | -7.74 | chr12-123630252-G-A |
| 76 | R→Q | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.60) | -5.36 | COSV99967535 |
| 77 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630247-T-TC |
| 77 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630247-TC-T |
| 77 | G→R | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.99) | -7.71 | ClinVar:3087891 |
| 78 | E→K | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.14) | -5.37 | chr12-123630246-C-T |
| 78 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630246-CT-C |
| 78 | E→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2846761 |
| 79 | L→V | missense_variant | gnomAD | — | 4.10e-06 | — | likely_benign (0.11) | -0.34 | chr12-123630243-G-C |
| 81 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123630235-G-A |
| 81 | L→P | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.97) | -9.60 | chr12-123630236-A-G |
| 82 | R→S | missense_variant | gnomAD | — | 2.05e-06 | — | likely_benign (0.20) | -2.34 | chr12-123630232-C-A |
| 83 | — | inframe_deletion | gnomAD | — | 7.52e-06 | — | — | — | chr12-123630229-TCTC-T |
| 83 | R→T | missense_variant | gnomAD | — | 6.84e-06 | — | ambiguous (0.46) | -3.03 | chr12-123630230-C-G |
| 83 | R→K | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | 3.09 | chr12-123630230-C-T |
| 83 | — | inframe_deletion | ClinVar | Uncertain significance | — | — | — | — | ClinVar:1933346 |
| 83 | R→G | missense_variant | COSMIC | — | — | — | ambiguous (0.50) | -6.78 | COSV99967524 |
| 84 | I→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.11) | -3.22 | chr12-123630228-T-C |
| 85 | S→S | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123630223-T-A |
| 85 | S→P | missense_variant | gnomAD | — | 3.42e-06 | damaging | likely_pathogenic (0.68) | -7.69 | chr12-123630225-A-G |
| 85 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2991250 |
| 86 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630222-G-A |
| 87 | S→S | synonymous_variant | gnomAD | — | 6.16e-06 | — | — | 0.00 | chr12-123630217-T-C |
| 87 | S→S | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123630217-T-G |
| 87 | S→L | missense_variant | gnomAD | — | 5.47e-06 | damaging | ambiguous (0.56) | -7.56 | chr12-123630218-G-A |
| 87 | S→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630218-G-C |
| 87 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1632053 |
| 87 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1938791 |
| 87 | S→L | missense_variant | ClinVar | Uncertain significance | — | damaging | ambiguous (0.56) | -7.56 | ClinVar:1964945 |
| 87 | S→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2719446 |
| 88 | R→I | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.91) | -10.49 | chr12-123630215-C-A |
| 88 | R→K | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.53) | -6.06 | chr12-123630215-C-T |
| 88 | R→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630216-T-A |
| 88 | R→G | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.85) | -7.99 | chr12-123630216-T-C |
| 89 | N→N | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630211-G-A |
| 90 | K→E | missense_variant | ClinVar | Pathogenic | — | — | ambiguous (0.46) | -6.91 | ClinVar:217279 |
| 91 | I→I | synonymous_variant | gnomAD | — | 8.21e-06 | — | — | 0.00 | chr12-123630205-A-G |
| 91 | I→T | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.61) | -5.74 | chr12-123630206-A-G |
| 91 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630206-AT-A |
| 93 | D→D | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123630199-A-G |
| 93 | D→Y | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.15) | -3.72 | chr12-123630201-C-A |
| 93 | D→D | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2753789 |
| 94 | L→P | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.93) | -9.08 | chr12-123630197-A-G |
| 94 | L→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -5.52 | chr12-123630198-G-C |
| 95 | C→C | synonymous_variant | gnomAD | — | 6.16e-06 | — | — | 0.00 | chr12-123630193-G-A |
| 95 | C→C | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3003887 |
| 96 | H→H | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123630190-A-G |
| 96 | H→L | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -5.74 | chr12-123630191-T-A |
| 96 | H→D | missense_variant | gnomAD | — | 2.74e-06 | — | likely_benign (0.25) | -7.18 | chr12-123630192-G-C |
| 96 | H→N | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.10) | -5.30 | chr12-123630192-G-T |
| 96 | H→H | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2701929 |
| 97 | T→A | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.07) | -2.87 | chr12-123630189-T-C |
| 98 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123630184-G-GA |
| 98 | — | inframe_deletion | gnomAD | — | 1.37e-06 | — | — | — | chr12-123630184-GAAA-G |
| 99 | I→F | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.50) | -7.47 | chr12-123630183-T-A |
| 99 | I→L | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.23) | -6.41 | ClinVar:3380131 |
| 100 | K→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.26) | -4.88 | chr12-123630179-T-G |
| 100 | K→E | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.30) | -4.97 | chr12-123630180-T-C |
| 101 | D→D | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2891533 |
| 102 | G→G | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123630172-T-C |
| 102 | G→G | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123630172-T-G |
| 102 | G→E | missense_variant | gnomAD | — | 3.63e-05 | damaging | likely_pathogenic (0.58) | -2.85 | chr12-123630173-C-T |
| 102 | G→G | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2845940 |
| 103 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123630169-C-A |
| 103 | A→A | synonymous_variant | gnomAD | — | 1.37e-05 | — | — | 0.00 | chr12-123630169-C-T |
| 103 | A→V | missense_variant | gnomAD | — | 1.10e-05 | — | likely_benign (0.25) | -4.46 | chr12-123630170-G-A |
| 103 | A→A | synonymous_variant | ClinVar | — | — | — | — | 0.00 | ClinVar:4381678 |
| 103 | A→V | missense_variant | COSMIC | — | — | — | likely_benign (0.25) | -4.46 | COSV108005073 |
| 104 | T→T | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627154-T-C |
| 104 | T→A | missense_variant | gnomAD | — | 1.98e-05 | — | likely_benign (0.11) | -4.25 | chr12-123627156-T-C |
| 105 | I→L | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.30) | -5.37 | chr12-123627153-T-A |
| 105 | I→V | missense_variant | gnomAD | — | 8.21e-06 | — | likely_benign (0.09) | -1.56 | chr12-123627153-T-C |
| 105 | I→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.09) | -1.56 | ClinVar:4017108 |
| 106 | L→F | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.41) | -6.32 | chr12-123627148-C-A |
| 106 | L→S | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.98) | -11.47 | chr12-123627149-A-G |
| 106 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:721731 |
| 106 | L→L | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV101424582 |
| 107 | T→T | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123627145-A-C |
| 107 | T→T | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV71194134 |
| 108 | H→H | synonymous_variant | gnomAD | — | 4.86e-05 | — | — | 0.00 | chr12-123627142-G-A |
| 108 | — | frameshift_variant | gnomAD | — | 4.79e-06 | LoF | — | — | chr12-123627142-G-GT |
| 108 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2802843 |
| 108 | H→H | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2898580 |
| 108 | H→H | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV71194586 |
| 109 | A→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.91) | -7.55 | chr12-123627140-G-A |
| 109 | A→T | missense_variant | gnomAD | — | 2.39e-05 | — | ambiguous (0.52) | -2.23 | chr12-123627141-C-T |
| 109 | A→T | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.52) | -2.23 | ClinVar:2689011 |
| 109 | A→T | missense_variant | COSMIC | — | — | — | ambiguous (0.52) | -2.23 | COSV71193843 |
| 110 | Y→C | missense_variant | gnomAD | — | 2.05e-06 | — | likely_benign (0.14) | -2.72 | chr12-123627137-T-C |
| 110 | Y→C | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.14) | -2.72 | ClinVar:548549 |
| 111 | S→S | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123627133-G-A |
| 111 | S→F | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.99) | -10.62 | chr12-123627134-G-A |
| 111 | S→F | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.99) | -10.62 | ClinVar:3068028 |
| 111 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:4766714 |
| 112 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627130-T-C |
| 112 | R→K | missense_variant | COSMIC | — | — | — | ambiguous (0.35) | -6.37 | COSV107522310 |
| 113 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627127-C-T |
| 114 | V→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.89) | -6.65 | chr12-123627126-C-G |
| 114 | V→L | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.89) | -6.65 | ClinVar:4743250 |
| 114 | V→F | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.93) | -9.55 | COSV71194509 |
| 115 | L→V | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.17) | -6.18 | chr12-123627123-G-C |
| 117 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627115-G-C |
| 117 | V→V | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV71194283 |
| 118 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627112-C-G |
| 118 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123627112-C-T |
| 118 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2820826 |
| 119 | E→E | synonymous_variant | gnomAD | — | 8.13e-04 | — | — | 0.00 | chr12-123627109-T-C |
| 119 | E→V | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.39) | -7.38 | chr12-123627110-T-A |
| 119 | E→E | synonymous_variant | ClinVar | Benign | — | — | — | 0.00 | ClinVar:307529 |
| 121 | A→A | synonymous_variant | gnomAD | — | 1.03e-05 | — | — | 0.00 | chr12-123627103-G-A |
| 121 | A→V | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.60) | -6.40 | chr12-123627104-G-A |
| 121 | A→T | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.54) | -6.05 | chr12-123627105-C-T |
| 121 | A→V | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.60) | -6.40 | ClinVar:1465594 |
| 121 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1650516 |
| 121 | A→V | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.60) | -6.40 | COSV71194272 |
| 122 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627100-C-T |
| 122 | V→L | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.22) | -5.05 | chr12-123627102-C-G |
| 122 | V→M | missense_variant | gnomAD | — | 3.22e-05 | — | likely_benign (0.17) | -5.62 | chr12-123627102-C-T |
| 122 | V→M | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.17) | -5.62 | ClinVar:1486551 |
| 123 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627097-C-G |
| 123 | A→A | synonymous_variant | gnomAD | — | 9.47e-04 | — | — | 0.00 | chr12-123627097-C-T |
| 123 | A→V | missense_variant | gnomAD | — | 1.30e-05 | — | likely_benign (0.09) | -2.58 | chr12-123627098-G-A |
| 123 | A→A | synonymous_variant | ClinVar | Benign/Likely benign | — | — | — | 0.00 | ClinVar:425020 |
| 123 | A→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.09) | -2.58 | ClinVar:1467898 |
| 124 | A→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.14) | -5.05 | chr12-123627095-G-A |
| 124 | A→T | missense_variant | gnomAD | — | 1.85e-05 | — | likely_benign (0.10) | -4.61 | chr12-123627096-C-T |
| 124 | A→T | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.10) | -4.61 | ClinVar:806960 |
| 124 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2018522 |
| 124 | A→G | missense_variant | COSMIC | — | — | — | likely_benign (0.12) | -4.33 | COSV71194527 |
| 124 | A→T | missense_variant | COSMIC | — | — | — | likely_benign (0.10) | -4.61 | COSV71193807 |
| 125 | K→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123627093-T-A |
| 125 | K→N | missense_variant | COSMIC | — | — | — | likely_benign (0.24) | -2.37 | COSV101424580 |
| 126 | K→M | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.59) | -8.62 | chr12-123627089-T-A |
| 127 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627085-T-C |
| 127 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627085-T-G |
| 127 | R→Q | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.23) | -4.65 | chr12-123627086-C-T |
| 127 | R→* | stop_gained | gnomAD | — | 8.55e-05 | LoF | — | — | chr12-123627087-G-A |
| 127 | R→* | stop_gained | ClinVar | Pathogenic/Likely pathogenic | — | LoF | — | — | ClinVar:995942 |
| 127 | R→R | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2826822 |
| 127 | R→Q | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.23) | -4.65 | ClinVar:3087892 |
| 127 | R→Q | missense_variant | COSMIC | — | — | — | likely_benign (0.23) | -4.65 | COSV71193772 |
| 127 | R→* | stop_gained | COSMIC | — | — | LoF | — | — | COSV101424587 |
| 128 | F→L | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.95) | -4.94 | ClinVar:3087893 |
| 129 | S→S | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627079-A-G |
| 129 | S→I | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.19) | -5.87 | chr12-123627080-C-A |
| 129 | S→T | missense_variant | gnomAD | — | 2.74e-06 | — | likely_benign (0.07) | -2.19 | chr12-123627080-C-G |
| 129 | S→N | missense_variant | gnomAD | — | 2.53e-05 | — | likely_benign (0.12) | -2.47 | chr12-123627080-C-T |
| 129 | S→G | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -6.96 | chr12-123627081-T-C |
| 130 | V→V | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123627076-T-C |
| 130 | V→A | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.65) | -6.86 | chr12-123627077-A-G |
| 130 | V→L | missense_variant | gnomAD | — | 1.09e-05 | damaging | likely_pathogenic (0.71) | -6.49 | chr12-123627078-C-A |
| 130 | V→I | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.14) | -4.55 | chr12-123627078-C-T |
| 130 | V→A | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.65) | -6.86 | ClinVar:1703884 |
| 130 | V→L | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.71) | -6.49 | ClinVar:2198556 |
| 130 | V→A | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.65) | -6.86 | COSV71194221 |
| 131 | Y→Y | synonymous_variant | gnomAD | — | 8.89e-06 | — | — | 0.00 | chr12-123627073-G-A |
| 131 | Y→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123627073-G-T |
| 131 | Y→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2126425 |
| 131 | Y→Y | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3607656 |
| 132 | V→V | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123627070-G-A |
| 132 | V→I | missense_variant | gnomAD | — | 9.58e-06 | — | likely_benign (0.08) | -2.99 | chr12-123627072-C-T |
| 132 | V→I | missense_variant | ClinVar | Likely benign | — | — | likely_benign (0.08) | -2.99 | ClinVar:2604486 |
| 132 | V→I | missense_variant | COSMIC | — | — | — | likely_benign (0.08) | -2.99 | COSV107522311 |
| 133 | T→P | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.79) | -7.84 | ClinVar:3274962 |
| 134 | E→D | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.72) | -6.18 | chr12-123627064-C-G |
| 134 | E→E | synonymous_variant | gnomAD | — | 4.79e-06 | — | — | 0.00 | chr12-123627064-C-T |
| 134 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123627066-CTG-C |
| 134 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2765961 |
| 134 | E→E | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2898481 |
| 135 | S→* | stop_gained | gnomAD | — | 4.10e-06 | LoF | — | — | chr12-123627062-G-C |
| 135 | S→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.22) | -3.59 | chr12-123627063-A-C |
| 135 | — | frameshift_variant | ClinVar | Pathogenic/Likely pathogenic | — | LoF | — | — | ClinVar:2835749 |
| 136 | Q→Q | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123627058-C-T |
| 136 | Q→P | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.71) | -5.71 | chr12-123627059-T-G |
| 136 | Q→Q | synonymous_variant | ClinVar | Uncertain significance | — | — | — | 0.00 | ClinVar:883543 |
| 137 | P→H | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.91) | -8.12 | COSV101424581 |
| 138 | D→H | missense_variant | gnomAD | — | 1.09e-05 | damaging | likely_pathogenic (0.86) | -6.56 | chr12-123627054-C-G |
| 139 | L→F | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.09) | -2.35 | chr12-123627049-C-A |
| 139 | L→F | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | -2.35 | chr12-123627049-C-G |
| 139 | L→W | missense_variant | gnomAD | — | 2.74e-06 | — | likely_benign (0.16) | -4.52 | chr12-123627050-A-C |
| 139 | L→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | -2.87 | chr12-123627051-A-C |
| 139 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123627051-A-G |
| 139 | L→M | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.08) | -1.09 | chr12-123627051-A-T |
| 140 | S→S | synonymous_variant | gnomAD | — | 2.12e-05 | — | — | 0.00 | chr12-123627046-T-C |
| 140 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1570253 |
| 141 | G→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.98) | -9.75 | chr12-123627044-C-A |
| 142 | K→N | missense_variant | gnomAD | — | 2.19e-05 | — | ambiguous (0.37) | -3.54 | chr12-123626490-C-A |
| 142 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123626492-TACTG-T |
| 144 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123626485-AT-A |
| 145 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123626481-G-T |
| 145 | A→P | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.98) | -11.39 | chr12-123626483-C-G |
| 145 | A→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.20) | -4.33 | chr12-123626483-C-T |
| 145 | A→V | missense_variant | COSMIC | — | — | — | likely_benign (0.23) | -2.91 | COSV71194576 |
| 145 | A→T | missense_variant | COSMIC | — | — | — | likely_benign (0.20) | -4.33 | COSV109442771 |
| 146 | K→R | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.07) | -3.06 | chr12-123626479-T-C |
| 146 | K→E | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.07) | -1.34 | chr12-123626480-T-C |
| 147 | A→A | synonymous_variant | gnomAD | — | 1.78e-05 | — | — | 0.00 | chr12-123626475-G-A |
| 147 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2961832 |
| 148 | L→P | missense_variant | gnomAD | — | 3.42e-06 | damaging | likely_pathogenic (0.99) | -10.50 | chr12-123626473-A-G |
| 148 | L→F | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.72) | -8.12 | chr12-123626474-G-A |
| 148 | L→V | missense_variant | gnomAD | — | 4.10e-06 | — | ambiguous (0.40) | -7.31 | chr12-123626474-G-C |
| 148 | L→V | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.40) | -7.31 | ClinVar:3087894 |
| 148 | L→P | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.99) | -10.50 | ClinVar:3779607 |
| 148 | L→R | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.98) | -10.75 | COSV71194199 |
| 150 | H→H | synonymous_variant | gnomAD | — | 1.23e-05 | — | — | 0.00 | chr12-123626466-G-A |
| 150 | H→H | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1982698 |
| 150 | H→H | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV105350625 |
| 151 | L→F | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.15) | -4.68 | chr12-123626465-G-A |
| 151 | L→V | missense_variant | gnomAD | — | 4.10e-06 | — | likely_benign (0.14) | -6.18 | chr12-123626465-G-C |
| 151 | L→F | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.15) | -4.68 | ClinVar:3087895 |
| 152 | N→N | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123626460-G-A |
| 152 | N→S | missense_variant | gnomAD | — | 6.84e-06 | — | likely_benign (0.08) | -3.36 | chr12-123626461-T-C |
| 152 | N→S | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.08) | -3.36 | ClinVar:3274960 |
| 153 | V→V | synonymous_variant | gnomAD | — | 3.42e-06 | — | — | 0.00 | chr12-123626457-G-A |
| 153 | V→F | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.62) | -9.53 | chr12-123626459-C-A |
| 153 | V→I | missense_variant | gnomAD | — | 2.94e-05 | — | likely_benign (0.07) | -0.68 | chr12-123626459-C-T |
| 153 | V→I | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.07) | -0.68 | ClinVar:2182346 |
| 155 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123626453-CAG-C |
| 155 | V→D | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.94) | -12.23 | ClinVar:915406 |
| 155 | — | frameshift_variant | ClinVar | Likely pathogenic | — | LoF | — | — | ClinVar:3382064 |
| 156 | T→T | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123626448-A-G |
| 156 | T→S | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.24) | -5.38 | chr12-123626449-G-C |
| 156 | T→S | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.24) | -5.38 | chr12-123626450-T-A |
| 156 | T→S | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.24) | -5.38 | ClinVar:3274961 |
| 157 | V→M | missense_variant | gnomAD | — | 4.10e-06 | — | likely_benign (0.15) | -2.46 | chr12-123626447-C-T |
| 158 | V→V | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123626442-C-T |
| 158 | V→L | missense_variant | gnomAD | — | 5.47e-06 | — | ambiguous (0.37) | -4.80 | chr12-123626444-C-G |
| 158 | V→M | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.49) | -5.64 | chr12-123626444-C-T |
| 158 | V→L | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.37) | -4.80 | ClinVar:2178158 |
| 158 | V→M | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.49) | -5.64 | ClinVar:1977645 |
| 158 | V→L | missense_variant | COSMIC | — | — | — | ambiguous (0.37) | -4.80 | COSV71194730 |
| 159 | L→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.26) | -4.84 | ClinVar:4618336 |
| 160 | D→G | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.98) | -10.00 | chr12-123626437-T-C |
| 161 | A→A | synonymous_variant | gnomAD | — | 1.04e-04 | — | — | 0.00 | chr12-123626433-A-G |
| 161 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123626433-A-T |
| 161 | A→T | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.24) | -5.07 | chr12-123626435-C-T |
| 161 | A→A | synonymous_variant | ClinVar | Conflicting classifications of pathogenicity | — | — | — | 0.00 | ClinVar:882754 |
| 161 | A→A | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV107522313 |
| 161 | A→T | missense_variant | COSMIC | — | — | — | likely_benign (0.24) | -5.07 | COSV71194288 |
| 162 | A→A | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123626430-A-T |
| 162 | A→T | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.60) | -6.18 | chr12-123626432-C-T |
| 163 | V→V | synonymous_variant | gnomAD | — | 1.71e-05 | — | — | 0.00 | chr12-123626427-G-A |
| 163 | V→V | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123626427-G-T |
| 163 | V→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.19) | -5.82 | chr12-123626428-A-G |
| 163 | V→I | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.12) | -4.13 | chr12-123626429-C-T |
| 163 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123626429-CAGCAGCATCT-C |
| 163 | V→F | missense_variant | ClinVar | Pathogenic | — | damaging | likely_pathogenic (0.72) | -10.04 | ClinVar:217277 |
| 163 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2977464 |
| 163 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2983669 |
| 164 | G→G | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624862-G-A |
| 164 | G→D | missense_variant | gnomAD | — | 1.09e-05 | damaging | likely_pathogenic (0.98) | -8.24 | chr12-123626425-C-T |
| 164 | G→S | missense_variant | gnomAD | — | 1.57e-05 | — | likely_benign (0.29) | -5.30 | chr12-123626426-C-T |
| 164 | G→D | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.98) | -8.24 | ClinVar:977417 |
| 165 | Y→C | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.32) | -6.33 | chr12-123624860-T-C |
| 166 | I→V | missense_variant | gnomAD | — | 5.47e-06 | — | likely_benign (0.07) | -2.25 | chr12-123624858-T-C |
| 167 | M→I | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.59) | -3.88 | chr12-123624853-C-T |
| 167 | M→T | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.72) | -6.03 | chr12-123624854-A-G |
| 168 | E→D | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.49) | -4.36 | chr12-123624850-C-G |
| 168 | E→* | stop_gained | ClinVar | — | — | LoF | — | — | ClinVar:4381676 |
| 168 | E→* | stop_gained | COSMIC | — | — | LoF | — | — | COSV99434892 |
| 169 | K→K | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624847-T-C |
| 169 | K→R | missense_variant | gnomAD | — | 1.44e-05 | — | likely_benign (0.10) | -4.16 | chr12-123624848-T-C |
| 169 | K→E | missense_variant | gnomAD | — | 7.53e-06 | — | likely_benign (0.31) | -6.94 | chr12-123624849-T-C |
| 169 | K→E | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.31) | -6.94 | ClinVar:1432529 |
| 169 | K→K | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2744942 |
| 170 | A→E | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.88) | -6.34 | chr12-123624845-G-T |
| 171 | D→H | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.68) | -6.23 | chr12-123624843-C-G |
| 171 | D→N | missense_variant | gnomAD | — | 1.51e-05 | — | likely_benign (0.25) | -4.95 | chr12-123624843-C-T |
| 173 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624835-G-T |
| 173 | V→I | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.12) | -4.26 | chr12-123624837-C-T |
| 173 | V→I | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.12) | -4.26 | ClinVar:1696202 |
| 173 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2839826 |
| 174 | I→T | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.85) | -8.33 | chr12-123624833-A-G |
| 174 | I→L | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.07) | -2.57 | chr12-123624834-T-A |
| 175 | V→V | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123624829-A-G |
| 175 | V→I | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.19) | -5.40 | chr12-123624831-C-T |
| 175 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2997166 |
| 176 | G→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -11.00 | chr12-123624827-C-A |
| 176 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123624828-C-CA |
| 176 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:1416368 |
| 177 | A→G | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.57) | -6.99 | chr12-123624824-G-C |
| 177 | — | frameshift_variant | gnomAD | — | 8.89e-06 | LoF | — | — | chr12-123624824-GCA-G |
| 177 | — | frameshift_variant | ClinVar | Pathogenic/Likely pathogenic | — | LoF | — | — | ClinVar:1176971 |
| 179 | G→G | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624817-T-A |
| 179 | G→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.92) | -7.68 | chr12-123624818-C-A |
| 179 | G→R | missense_variant | gnomAD | — | 3.42e-06 | damaging | likely_pathogenic (1.00) | -8.93 | chr12-123624819-C-T |
| 181 | V→A | missense_variant | gnomAD | — | 7.53e-06 | — | ambiguous (0.41) | -5.17 | chr12-123624812-A-G |
| 181 | V→F | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.87) | -9.11 | chr12-123624813-C-A |
| 181 | V→A | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.41) | -5.17 | ClinVar:1373531 |
| 183 | N→N | synonymous_variant | gnomAD | — | 7.66e-05 | — | — | 0.00 | chr12-123624805-G-A |
| 183 | N→N | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:715309 |
| 183 | N→S | missense_variant | COSMIC | — | — | — | likely_benign (0.11) | 3.07 | COSV99434254 |
| 184 | G→R | missense_variant | gnomAD | — | 1.64e-05 | damaging | likely_pathogenic (0.99) | -10.12 | chr12-123624804-C-T |
| 184 | G→R | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.99) | -10.12 | ClinVar:1981639 |
| 185 | G→G | synonymous_variant | gnomAD | — | 7.53e-06 | — | — | 0.00 | chr12-123624799-T-G |
| 185 | G→G | synonymous_variant | ClinVar | Uncertain significance | — | — | — | 0.00 | ClinVar:882753 |
| 186 | I→I | synonymous_variant | gnomAD | — | 1.03e-05 | — | — | 0.00 | chr12-123624796-A-G |
| 186 | I→S | missense_variant | gnomAD | — | 2.74e-06 | damaging | likely_pathogenic (0.98) | -9.38 | chr12-123624797-A-C |
| 186 | I→T | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.97) | -6.29 | chr12-123624797-A-G |
| 186 | — | inframe_deletion | ClinVar | Pathogenic | — | — | — | — | ClinVar:217280 |
| 186 | I→I | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3010734 |
| 187 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624793-A-G |
| 187 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123624793-A-T |
| 187 | I→I | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:740083 |
| 187 | I→I | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3700710 |
| 188 | N→Y | missense_variant | gnomAD | — | 1.64e-05 | damaging | likely_pathogenic (0.98) | -11.44 | chr12-123624792-T-A |
| 188 | N→H | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.87) | -9.81 | chr12-123624792-T-G |
| 188 | N→Y | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.98) | -11.44 | ClinVar:4124 |
| 189 | K→N | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.95) | -6.80 | chr12-123624787-C-G |
| 189 | K→N | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.95) | -6.80 | ClinVar:982930 |
| 190 | I→M | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.30) | -4.94 | chr12-123622759-A-C |
| 190 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622759-A-G |
| 191 | G→V | missense_variant | gnomAD | — | 2.26e-05 | damaging | likely_pathogenic (1.00) | -10.19 | chr12-123622757-C-A |
| 191 | G→R | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -10.31 | chr12-123622758-C-T |
| 192 | T→I | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -8.87 | chr12-123622754-G-A |
| 192 | T→N | missense_variant | gnomAD | — | 4.11e-06 | damaging | likely_pathogenic (0.94) | -10.37 | chr12-123622754-G-T |
| 192 | T→N | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.94) | -10.37 | ClinVar:2537812 |
| 193 | N→S | missense_variant | gnomAD | — | 1.92e-05 | — | likely_benign (0.08) | -1.97 | chr12-123622751-T-C |
| 196 | A→T | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.95) | -8.56 | chr12-123622743-C-T |
| 196 | A→T | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.95) | -8.56 | COSV108044470 |
| 196 | A→S | missense_variant | COSMIC | — | — | — | ambiguous (0.45) | -6.56 | COSV53017684 |
| 197 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622738-C-T |
| 197 | V→L | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.14) | -4.62 | chr12-123622740-C-A |
| 197 | V→M | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.15) | -5.55 | chr12-123622740-C-T |
| 197 | V→L | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.14) | -4.62 | ClinVar:3274963 |
| 198 | C→C | synonymous_variant | gnomAD | — | 1.85e-05 | — | — | 0.00 | chr12-123622735-A-G |
| 198 | C→Y | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.80) | -6.59 | chr12-123622736-C-T |
| 198 | C→R | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.96) | -10.68 | chr12-123622737-A-G |
| 198 | C→C | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2889787 |
| 199 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123622733-GCA-G |
| 199 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2829720 |
| 200 | K→N | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.76) | -6.16 | chr12-123622729-T-G |
| 200 | K→T | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.55) | -7.00 | chr12-123622730-T-G |
| 201 | A→V | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.12) | -3.78 | chr12-123622727-G-A |
| 201 | A→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.12) | -3.78 | ClinVar:1043126 |
| 202 | Q→Q | synonymous_variant | gnomAD | — | 1.16e-05 | — | — | 0.00 | chr12-123622723-C-T |
| 202 | Q→R | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.13) | -3.98 | chr12-123622724-T-C |
| 202 | Q→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123622725-G-A |
| 202 | Q→K | missense_variant | gnomAD | — | 2.74e-06 | — | likely_benign (0.17) | -4.77 | chr12-123622725-G-T |
| 202 | Q→Q | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2570853 |
| 203 | N→N | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123622720-G-A |
| 204 | K→R | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.16) | -4.99 | chr12-123622718-T-C |
| 204 | K→R | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.16) | -4.99 | ClinVar:882752 |
| 205 | P→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.73) | -6.70 | chr12-123622715-G-A |
| 206 | F→F | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622711-G-A |
| 206 | F→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.85) | -4.93 | chr12-123622713-A-G |
| 206 | F→L | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.85) | -4.93 | COSV108044475 |
| 207 | — | inframe_deletion | gnomAD | — | 6.84e-07 | — | — | — | chr12-123622708-ATAGAAAGGT-A |
| 207 | Y→C | missense_variant | gnomAD | — | 1.30e-05 | damaging | ambiguous (0.54) | -7.75 | chr12-123622709-T-C |
| 207 | Y→C | missense_variant | ClinVar | Uncertain significance | — | damaging | ambiguous (0.54) | -7.75 | ClinVar:1906761 |
| 208 | V→V | synonymous_variant | gnomAD | — | 5.47e-06 | — | — | 0.00 | chr12-123622705-C-T |
| 208 | V→A | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.43) | -5.68 | chr12-123622706-A-G |
| 208 | V→M | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.94) | -9.12 | chr12-123622707-C-T |
| 209 | V→A | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.26) | -5.42 | chr12-123622703-A-G |
| 210 | A→V | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.41) | -5.81 | chr12-123622700-G-A |
| 210 | A→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.18) | -4.00 | chr12-123622701-C-T |
| 211 | E→E | synonymous_variant | gnomAD | — | 4.79e-06 | — | — | 0.00 | chr12-123622696-T-C |
| 211 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123622697-TC-T |
| 211 | E→K | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.99) | -10.44 | chr12-123622698-C-T |
| 212 | S→S | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622693-A-G |
| 212 | S→N | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.92) | -8.19 | chr12-123622694-C-T |
| 212 | — | frameshift_variant | gnomAD | — | 4.10e-06 | LoF | — | — | chr12-123622694-CTT-C |
| 212 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2762330 |
| 213 | F→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.98) | -5.68 | chr12-123622692-A-G |
| 213 | F→F | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53015462 |
| 214 | K→N | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.99) | -9.12 | chr12-123622687-C-G |
| 214 | K→K | synonymous_variant | gnomAD | — | 7.52e-06 | — | — | 0.00 | chr12-123622687-C-T |
| 214 | K→M | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.99) | -9.87 | COSV53017385 |
| 215 | F→L | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (1.00) | -9.00 | chr12-123622686-A-G |
| 216 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123622683-CAAACTTG-C |
| 216 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2765937 |
| 217 | R→R | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622678-C-G |
| 217 | R→Q | missense_variant | gnomAD | — | 4.10e-06 | damaging | likely_pathogenic (0.81) | -7.75 | chr12-123622679-C-T |
| 217 | R→W | missense_variant | gnomAD | — | 4.79e-06 | damaging | likely_pathogenic (0.92) | -9.75 | chr12-123622680-G-A |
| 217 | R→W | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.92) | -9.75 | COSV53016012 |
| 218 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622675-G-C |
| 218 | L→P | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.97) | -9.96 | chr12-123622676-A-G |
| 218 | L→L | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV99434759 |
| 218 | L→P | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.97) | -9.96 | COSV53015966 |
| 218 | L→F | missense_variant | COSMIC | — | — | — | likely_benign (0.34) | -6.12 | COSV99434394 |
| 219 | F→L | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (1.00) | -7.96 | chr12-123622672-A-C |
| 219 | F→V | missense_variant | ClinVar | Pathogenic | — | damaging | likely_pathogenic (0.97) | -9.65 | ClinVar:217282 |
| 219 | F→F | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2781763 |
| 220 | P→R | missense_variant | gnomAD | — | 4.79e-06 | damaging | likely_pathogenic (0.99) | -12.31 | chr12-123622670-G-C |
| 220 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:1461865 |
| 221 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123622666-T-G |
| 221 | L→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.62) | -7.44 | chr12-123622668-G-C |
| 221 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2829479 |
| 222 | N→N | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123622663-G-A |
| 222 | N→K | missense_variant | gnomAD | — | 3.42e-06 | damaging | likely_pathogenic (0.79) | -6.92 | chr12-123622663-G-C |
| 222 | N→S | missense_variant | gnomAD | — | 2.05e-06 | — | likely_benign (0.11) | -4.32 | chr12-123622664-T-C |
| 222 | N→N | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2693620 |
| 223 | Q→Q | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123622660-C-T |
| 223 | Q→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123622662-G-A |
| 224 | Q→E | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.09) | -4.50 | chr12-123622659-G-C |
| 225 | D→D | synonymous_variant | gnomAD | — | 9.58e-06 | — | — | 0.00 | chr12-123622654-G-A |
| 225 | D→D | synonymous_variant | ClinVar | Conflicting classifications of pathogenicity | — | — | — | 0.00 | ClinVar:198774 |
| 226 | V→I | missense_variant | gnomAD | — | 3.35e-05 | — | likely_benign (0.09) | -2.43 | chr12-123622653-C-T |
| 226 | V→I | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.09) | -2.43 | ClinVar:2342295 |
| 226 | V→V | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV106362880 |
| 228 | D→G | missense_variant | gnomAD | — | 7.53e-06 | — | likely_benign (0.16) | -3.91 | chr12-123622646-T-C |
| 231 | K→R | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.17) | -3.94 | ClinVar:2584983 |
| 231 | K→N | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.99) | -6.51 | COSV104586314 |
| 232 | Y→* | stop_gained | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123621918-A-C |
| 232 | Y→C | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.81) | -4.74 | chr12-123621919-T-C |
| 233 | K→E | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.31) | -5.13 | chr12-123621917-T-C |
| 234 | A→T | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.12) | -2.46 | ClinVar:4017109 |
| 235 | D→D | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123621909-G-A |
| 235 | D→D | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2892296 |
| 235 | D→Y | missense_variant | COSMIC | — | — | — | likely_benign (0.20) | -4.08 | COSV53016683 |
| 237 | L→L | synonymous_variant | gnomAD | — | 8.55e-05 | — | — | 0.00 | chr12-123621903-G-A |
| 237 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123621903-G-C |
| 237 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:3013246 |
| 238 | K→K | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621900-C-T |
| 238 | K→R | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.07) | -2.24 | chr12-123621901-T-C |
| 238 | — | frameshift_variant | gnomAD | — | 6.16e-06 | LoF | — | — | chr12-123621902-TGA-T |
| 238 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:1683289 |
| 239 | V→V | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621897-G-A |
| 239 | V→V | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123621897-G-C |
| 239 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1616596 |
| 239 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2787901 |
| 240 | A→A | synonymous_variant | gnomAD | — | 2.67e-05 | — | — | 0.00 | chr12-123621894-C-T |
| 240 | A→V | missense_variant | gnomAD | — | 1.71e-05 | — | likely_benign (0.08) | -1.77 | chr12-123621895-G-A |
| 240 | — | frameshift_variant | gnomAD | — | 7.53e-06 | LoF | — | — | chr12-123621896-C-CGACCT |
| 240 | A→T | missense_variant | gnomAD | — | 8.62e-05 | — | likely_benign (0.07) | -1.92 | chr12-123621896-C-T |
| 240 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:762889 |
| 240 | A→T | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.07) | -1.92 | ClinVar:1524276 |
| 240 | A→V | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.08) | -1.77 | ClinVar:2140196 |
| 240 | — | frameshift_variant | ClinVar | Pathogenic/Likely pathogenic | — | LoF | — | — | ClinVar:2891124 |
| 240 | A→A | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53016619 |
| 240 | A→V | missense_variant | COSMIC | — | — | — | likely_benign (0.08) | -1.77 | COSV53015723 |
| 240 | A→S | missense_variant | COSMIC | — | — | — | likely_benign (0.07) | -2.48 | COSV99434053 |
| 241 | Q→* | stop_gained | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123621893-G-A |
| 241 | Q→E | missense_variant | gnomAD | — | 2.74e-06 | — | likely_benign (0.06) | -1.95 | chr12-123621893-G-C |
| 241 | Q→K | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.06) | 0.23 | chr12-123621893-G-T |
| 242 | T→T | synonymous_variant | gnomAD | — | 1.09e-05 | — | — | 0.00 | chr12-123621888-A-G |
| 242 | T→T | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2984521 |
| 243 | G→V | missense_variant | COSMIC | — | — | — | likely_benign (0.12) | -4.64 | COSV53017342 |
| 245 | D→A | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.13) | -4.20 | chr12-123621880-T-G |
| 245 | D→N | missense_variant | gnomAD | — | 1.37e-06 | — | likely_benign (0.07) | -0.44 | chr12-123621881-C-T |
| 246 | L→I | missense_variant | COSMIC | — | — | — | likely_benign (0.12) | -5.25 | COSV99434871 |
| 247 | K→K | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621873-T-C |
| 247 | K→R | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.07) | 2.47 | chr12-123621874-T-C |
| 247 | K→T | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.08) | 0.98 | chr12-123621874-T-G |
| 247 | K→Q | missense_variant | gnomAD | — | 3.42e-06 | — | likely_benign (0.09) | -0.44 | chr12-123621875-T-G |
| 248 | E→E | synonymous_variant | gnomAD | — | 8.21e-06 | — | — | 0.00 | chr12-123621870-C-T |
| 248 | E→Q | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.09) | -1.53 | chr12-123621872-C-G |
| 248 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123621872-CTT-C |
| 248 | E→E | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2898199 |
| 248 | E→Q | missense_variant | COSMIC | — | — | — | likely_benign (0.09) | -1.53 | COSV99434770 |
| 249 | E→E | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621867-C-T |
| 249 | E→G | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.22) | -4.85 | chr12-123621868-T-C |
| 249 | E→E | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2824669 |
| 250 | H→H | synonymous_variant | gnomAD | — | 4.79e-06 | — | — | 0.00 | chr12-123621864-A-G |
| 250 | H→Y | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.55) | -5.26 | chr12-123621866-G-A |
| 250 | H→D | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.78) | -8.23 | chr12-123621866-G-C |
| 251 | P→P | synonymous_variant | gnomAD | — | 2.05e-05 | — | — | 0.00 | chr12-123621861-C-T |
| 251 | P→L | missense_variant | gnomAD | — | 2.74e-06 | damaging | likely_pathogenic (0.88) | -6.53 | chr12-123621862-G-A |
| 251 | P→P | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:738949 |
| 251 | — | frameshift_variant | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:2769348 |
| 251 | P→P | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53016848 |
| 252 | W→* | stop_gained | ClinVar | Pathogenic | — | LoF | — | — | ClinVar:4700314 |
| 253 | V→V | synonymous_variant | gnomAD | — | 3.15e-05 | — | — | 0.00 | chr12-123621855-G-A |
| 253 | V→V | synonymous_variant | gnomAD | — | 2.74e-06 | — | — | 0.00 | chr12-123621855-G-C |
| 253 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1667617 |
| 253 | V→I | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.13) | 1.34 | ClinVar:1906251 |
| 253 | V→V | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1917279 |
| 253 | V→V | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53017155 |
| 254 | D→N | missense_variant | gnomAD | — | 8.89e-06 | damaging | likely_pathogenic (0.98) | -9.50 | chr12-123621854-C-T |
| 254 | D→H | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (1.00) | -12.12 | ClinVar:1465208 |
| 254 | D→D | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53016416 |
| 255 | Y→Y | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621849-G-A |
| 255 | Y→C | missense_variant | gnomAD | — | 3.56e-05 | damaging | likely_pathogenic (0.87) | -7.33 | chr12-123621850-T-C |
| 255 | Y→H | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.96) | -6.68 | chr12-123621851-A-G |
| 255 | Y→C | missense_variant | ClinVar | Pathogenic/Likely pathogenic | — | damaging | likely_pathogenic (0.87) | -7.33 | ClinVar:217281 |
| 255 | Y→F | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.20) | -5.05 | ClinVar:4740486 |
| 256 | T→T | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2719607 |
| 257 | A→P | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.08) | 0.39 | chr12-123621845-C-G |
| 258 | P→R | missense_variant | ClinVar | Pathogenic | — | damaging | likely_pathogenic (0.96) | -11.12 | ClinVar:217278 |
| 258 | P→A | missense_variant | ClinVar | Uncertain significance | — | — | ambiguous (0.43) | -6.02 | ClinVar:4017107 |
| 258 | P→A | missense_variant | COSMIC | — | — | — | ambiguous (0.43) | -6.02 | COSV99434579 |
| 259 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2823944 |
| 260 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123621834-TAAGG-T |
| 260 | L→V | missense_variant | gnomAD | — | 1.03e-05 | damaging | likely_benign (0.30) | -7.73 | chr12-123621836-A-C |
| 261 | I→I | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621831-G-A |
| 261 | — | frameshift_variant | gnomAD | — | 2.05e-06 | LoF | — | — | chr12-123621832-AT-A |
| 261 | I→V | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.17) | -5.24 | chr12-123621833-T-C |
| 262 | T→T | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621828-A-G |
| 262 | T→I | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.95) | -8.38 | chr12-123621829-G-A |
| 262 | — | frameshift_variant | gnomAD | — | 1.37e-06 | LoF | — | — | chr12-123621829-G-GTGAT |
| 263 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621827-G-A |
| 263 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2797947 |
| 264 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621822-C-G |
| 264 | L→L | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123621822-C-T |
| 264 | L→Q | missense_variant | gnomAD | — | 4.10e-06 | damaging | likely_pathogenic (0.97) | -10.62 | chr12-123621823-A-T |
| 264 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2801144 |
| 265 | F→F | synonymous_variant | gnomAD | — | 2.05e-06 | — | — | 0.00 | chr12-123621819-A-G |
| 265 | — | inframe_deletion | gnomAD | — | 6.84e-07 | — | — | — | chr12-123621821-ACAG-A |
| 266 | T→I | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (1.00) | -8.87 | chr12-123621817-G-A |
| 266 | — | frameshift_variant | gnomAD | — | 6.84e-07 | LoF | — | — | chr12-123621818-TA-T |
| 267 | D→G | missense_variant | gnomAD | — | 2.74e-06 | damaging | likely_pathogenic (0.99) | -10.12 | chr12-123621814-T-C |
| 267 | D→G | missense_variant | ClinVar | Conflicting classifications of pathogenicity | — | damaging | likely_pathogenic (0.99) | -10.12 | ClinVar:1426819 |
| 269 | G→G | synonymous_variant | gnomAD | — | 4.79e-06 | — | — | 0.00 | chr12-123621807-G-A |
| 269 | G→G | synonymous_variant | gnomAD | — | 1.71e-05 | — | — | 0.00 | chr12-123621807-G-C |
| 269 | G→S | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.92) | -8.87 | chr12-123621809-C-T |
| 269 | G→G | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2643513 |
| 269 | G→G | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2981686 |
| 269 | G→D | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.98) | -9.12 | COSV53016088 |
| 270 | V→M | missense_variant | gnomAD | — | 1.37e-05 | damaging | likely_pathogenic (0.64) | -6.99 | chr12-123621806-C-T |
| 270 | V→M | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.64) | -6.99 | ClinVar:307528 |
| 270 | V→A | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.69) | -5.52 | ClinVar:2130873 |
| 270 | V→M | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.64) | -6.99 | COSV53016408 |
| 271 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621801-C-A |
| 271 | L→L | synonymous_variant | gnomAD | — | 1.64e-05 | — | — | 0.00 | chr12-123621801-C-T |
| 271 | L→R | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.94) | -9.66 | chr12-123621802-A-C |
| 271 | L→P | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.99) | -9.79 | chr12-123621802-A-G |
| 271 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2992127 |
| 272 | T→I | missense_variant | gnomAD | — | 1.37e-06 | damaging | likely_pathogenic (0.92) | -7.30 | chr12-123621799-G-A |
| 272 | T→R | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.90) | -9.49 | chr12-123621799-G-C |
| 272 | T→R | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.90) | -9.49 | ClinVar:2584935 |
| 273 | P→S | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.82) | -6.94 | chr12-123621797-G-A |
| 274 | S→S | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621792-T-C |
| 275 | A→A | synonymous_variant | gnomAD | — | 4.11e-06 | — | — | 0.00 | chr12-123621789-T-G |
| 275 | A→T | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.85) | -7.55 | chr12-123621791-C-T |
| 275 | A→A | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1910644 |
| 276 | V→I | missense_variant | COSMIC | — | — | — | likely_benign (0.15) | -6.97 | COSV53018031 |
| 277 | S→S | synonymous_variant | gnomAD | — | 1.40e-04 | — | — | 0.00 | chr12-123621783-G-A |
| 277 | S→G | missense_variant | gnomAD | — | 6.84e-07 | — | likely_benign (0.34) | -7.31 | chr12-123621785-T-C |
| 277 | S→S | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:732578 |
| 277 | S→G | missense_variant | ClinVar | Uncertain significance | — | — | likely_benign (0.34) | -7.31 | ClinVar:4247692 |
| 277 | S→S | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV99434724 |
| 278 | D→D | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2105244 |
| 279 | E→D | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.97) | -8.62 | chr12-123621777-C-G |
| 279 | E→G | missense_variant | gnomAD | — | 2.74e-06 | damaging | likely_pathogenic (0.95) | -8.37 | chr12-123621778-T-C |
| 279 | E→D | missense_variant | ClinVar | Uncertain significance | — | damaging | likely_pathogenic (0.97) | -8.62 | ClinVar:1509586 |
| 280 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123621774-G-A |
| 280 | L→V | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.86) | -8.62 | chr12-123621776-G-C |
| 280 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2969477 |
| 281 | I→L | missense_variant | gnomAD | — | 6.84e-07 | — | ambiguous (0.46) | -6.90 | chr12-123621773-T-G |
| 281 | I→I | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:1579754 |
| 282 | — | inframe_deletion | gnomAD | — | 6.84e-07 | — | — | — | chr12-123621769-TTGA-T |
| 283 | L→L | synonymous_variant | gnomAD | — | 1.37e-06 | — | — | 0.00 | chr12-123621765-G-A |
| 283 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621765-G-C |
| 283 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2736177 |
| 283 | L→L | synonymous_variant | ClinVar | Likely benign | — | — | — | 0.00 | ClinVar:2844897 |
| 283 | L→F | missense_variant | COSMIC | — | — | damaging | likely_pathogenic (0.72) | -6.56 | COSV105107975 |
| 284 | Y→C | missense_variant | gnomAD | — | 2.05e-06 | damaging | likely_pathogenic (0.90) | -7.87 | chr12-123621763-T-C |
| 284 | Y→H | missense_variant | gnomAD | — | 6.84e-07 | damaging | likely_pathogenic (0.89) | -7.28 | chr12-123621764-A-G |
| 285 | L→L | synonymous_variant | gnomAD | — | 6.84e-07 | — | — | 0.00 | chr12-123621759-C-A |
| 285 | L→M | missense_variant | COSMIC | — | — | — | likely_benign (0.26) | -3.50 | COSV99434855 |
| 285 | L→L | synonymous_variant | COSMIC | — | — | — | — | 0.00 | COSV53017328 |
710 variants in the shared canonical core.
LoF = frameshift / stop-gain / splice-disrupting — inherently loss-of-function, flagged by consequence (AlphaMissense and ESM-C score only missense/substitutions, so they are blank here by design, not by absence of impact). AlphaMissense is computed in the canonical reading frame, so it scores the shared core but reads N/A across an isoform-unique extension — use ESM-C ΔLLR there.