SwissIsoform v2

CBX1 · ENST00000225603.9

EXTENDED 239 aa (canonical 185 aa) · UniProt P83916 · CDLMPS

chr17:48101392:-:GTG:ENST00000225603.9

AI summary A 55-aa N-terminal extension folds into a confident but unintegrated strand and shifts whole-protein hydropathy, without touching the chromodomain reader function.
How it diverges

The extension adds a 29-residue strand (pLDDT 0.83) that folds independently but shows essentially no contact with the shared CBX1 core (PAE ~30 Å to the body), so it reads as a dangling appendage rather than an integrated module; in parallel it shifts the whole protein toward higher hydropathy and lower fraction-charged, and a strong interpretable-feature shift accompanies it. Localization and domain architecture are unchanged: DeepLoc keeps both isoform and canonical nuclear (top_prob dropping from 0.93 to 0.80 but no compartment flip), and no real InterPro domain — including no chromodomain footprint — overlaps the added sequence. The large shared-region RMSD (9.73 Å) is not trustworthy as a core refold given low global pTM (0.34–0.39), so no genuine reorganization of the retained fold is supported.

Why it matters

CBX1's function rests entirely on its chromodomain reading H3K9me3 and its downstream partnerships (SUV39H1, PurB/Sp3, PRC2, KAP-1/Chk2), all located in the shared, unchanged C-terminal/core region — this extension neither gains nor loses a domain that would touch any of that machinery, and it does not relocalize the protein out of the nucleus. The added structured-but-disconnected strand and altered hydropathy/charge balance could plausibly tune solubility, aggregation propensity, or a novel unannotated interaction surface, but nothing in the differential findings ties this to H3K9me3 reading, heterochromatin nucleation, or DNA-damage-induced mobilization — the isoform's known biology is essentially untouched by this extension based on current evidence.

Structured N-terminal extensionBiophysical shiftInterpretable-feature shift
LLM confidence medium

The shared-region RMSD (9.73 Å) is likely placement uncertainty given low pTM (0.34-0.39), not tagged as a core refold. Extension unique-region conservation is real (phyloP 2.79, primate 91%) supporting translation as a genuine ORF, but germline/disease-variant signals are uninformative here (extension was intronic) and were excluded from the readout per instructions.

Folding

Canonical (185 aa)
Download CIF
Isoform (239 aa)
Download CIF
Coloured by ESMFold2 pLDDT confidence (blue = high, orange/red = low). Differential region — residues 1–54 (added in isoform) — 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 (1–54).

Evidence — click any tile for the differential-region detail

C Conservation Interesting
LLM reasoning
The N-terminal extension added ahead of the canonical CBX1 start is itself under real selective constraint, not just incidentally transcribed sequence: primate amino-acid identity across the unique region is 91.3% and mammalian identity 83.7% (versus 99.5% and 97.8% for the canonical protein at the same depths, so somewhat below the canonical baseline but still high), and absolute phyloP over the unique region is 2.79, above the ~2.0 strong-constraint threshold. The shared region is even more constrained (phyloP 4.95, enrichment ratio 0.56 favoring the shared region), which is expected since it is the ancestral coding sequence, but the unique region's own constraint level argues this extension is not just a passively transcribed, unconstrained 5'UTR-derived sequence — it has been under purifying selection in its own right across mammals and primates.
Unique region 91.3% similar across primates
Unique region 83.7% similar across mammals
Unique region PhyloP: 2.79 — purifying selection
D Detection Interesting
LLM reasoning
This N-terminal extension is a genuine, reproducibly-used alternative start site backed by direct peptide evidence, not just a computational prediction. The upstream TIS is detected in 5 of 6 cell lines with strong statistical support (e.g. K562 p=1.3e-12, U2OS p=9.3e-8), and initiation efficiency reaches 0.085 at its best (HeLa), well above the 0.01 threshold, indicating substantial ribosomal engagement relative to canonical initiation at this locus. Critically, one isoform-unique peptide spanning the extension (DATAATRLAAFLGATPPGDPTR) was PepQuery2-validated with a strong hyperscore (35.5) and low p-value (2e-4, 2 PSMs), directly confirming the extended N-terminus is translated into protein, not merely transcribed or ribosome-associated.
detected in 5/6 cell lines
Max Initiation Efficiency: 0.0846
1/11 isoform-unique peptides validated
L Localization Not interesting
LLM reasoning
Adding this 55-aa N-terminal segment does not redirect the protein: both isoform and canonical are predicted nuclear-localized with a nuclear localization signal retained and soluble membrane status unchanged, though the isoform's top-class probability is somewhat lower (0.796 vs 0.927). No secretory signal peptide or mitochondrial/chloroplast transit peptide is gained or lost — both canonical and isoform are classified 'OTHER'/'noTP' with no change in cleavage-site status. Neither compartment nor targeting-signal evidence supports a functional consequence for this extension.
iso: Nucleus | canon: Nucleus
iso: noTP | canon: noTP
M Mutation Landscape Not interesting
LLM reasoning
This is an N-terminal extension whose unique region was never-coding (intronic) sequence, so the germline depletion ratio and ESM-C constraint scores are uninformative by construction and cannot be read as protein constraint. The only valid readable signal — disease-variant density — argues against significance: zero ClinVar variants of any kind land in the unique region (n_matched=0), and only 4 COSMIC records do, each with just 1-2 samples, scattered across isoform positions 42/43/51/52 with no clustering. The pre-computed disease enrichment ratio (0.15) already showed depletion rather than concentration, and there are zero pathogenic ClinVar calls anywhere on this isoform (unique or shared). No hotspot, no recurrent somatic signal, no clinical burden — the data argues against a meaningful disease or functional signal in this region.
gnomAD variants 1.53× more in unique region — tolerant
Disease variants 6.49× less in unique region — depleted
P Predicted Structure Not interesting
LLM reasoning
The extension folds locally into a confident strand (residues 3-31, pLDDT 0.83) but this element is not integrated with the rest of the protein: PAE between it and the shared core (residues 56-239) averages 30.7 Å, and its only Ca contacts are with adjacent extension residues (1-2, 32-33) — none reach the core. Global pTM is low for both isoform (0.34) and canonical (0.39) predictions, and body-vs-body PAE within the shared region itself averages 18.2 Å with a wide spread, so the overall prediction's relative placements are largely unresolved. Given this, the large shared-region RMSD (9.73 Å) reported alongside a low pTM must be treated as placement uncertainty rather than a real refold, per the confidence gate. The net picture is a locally-folded but dangling extension with no evidence of docking against the core, and no reliable secondary signal of core reorganization — nothing here supports functional consequence.
pLDDT Differential Region: 0.762
Shared-Region RMSD: 9.73 Å
1 secondary structure identified in unique region
S Structural Characteristics Interesting
LLM reasoning
This N-terminal extension produces a measurable whole-protein biophysical shift alongside a strong shared-feature activation change, together suggesting the added 55-aa segment meaningfully alters the protein's overall physicochemical character even though it does not overlap any real InterPro domain. The whole-protein hydropathy delta (gravy +0.34) and fraction-charged delta (-0.07) both cross the scored threshold, consistent with the unique region being markedly more hydrophobic (GRAVY 0.23) and less charged (14.8% charged residues) than the shared canonical core (GRAVY -1.28, 46% charged) - a substantial compositional contrast at the new N-terminus. The sparse-autoencoder check also fires, with the strongest shared-feature activation shift (12.51) exceeding the 10.0 threshold, corroborating that the extension introduces a distinct sequence signature detected independently of the biophysical metrics. Domain architecture itself is unchanged - no real InterPro domains overlap the differential region, so this is not a domain-gain event - but the combined compositional and interpretability signal points to a functionally distinct N-terminal addition rather than inert sequence.
No diverging domains
more hydrophobic (+1.51) · less charged (-0.31) · less disordered (-0.13)
193 SAE features differ

Clinical variants

Differential region — N-terminal extension (isoform-unique)

Pos (iso) AA change Consequence Source Clin. sig. AF (gnomAD) Impact AlphaMissense ESM-C ΔLLR Link
1 R→G missense_variant gnomAD — 3.60e-06 — N/A -0.21 chr17-48101389-T-C
1 R→R synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101389-T-G
2 D→D synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101384-G-A
2 D→V missense_variant gnomAD — 2.40e-06 — N/A 0.30 chr17-48101385-T-A
2 D→G missense_variant gnomAD — 7.20e-06 — N/A 1.48 chr17-48101385-T-C
3 A→V missense_variant gnomAD — 2.40e-06 — N/A 0.55 chr17-48101382-G-A
3 A→S missense_variant gnomAD — 1.20e-06 — N/A -1.19 chr17-48101383-C-A
3 A→T missense_variant gnomAD — 9.60e-06 — N/A -1.50 chr17-48101383-C-T
5 A→A synonymous_variant gnomAD — 4.80e-06 — N/A 0.00 chr17-48101375-C-G
5 A→P missense_variant gnomAD — 1.20e-06 — N/A -0.52 chr17-48101377-C-G
5 A→T missense_variant gnomAD — 1.20e-06 — N/A -1.33 chr17-48101377-C-T
6 — inframe_insertion gnomAD — 1.32e-05 — N/A — chr17-48101372-G-GGCC
7 T→T synonymous_variant gnomAD — 2.40e-06 — N/A 0.00 chr17-48101369-G-C
7 — frameshift_variant gnomAD — 1.20e-06 LoF — — chr17-48101371-TG-T
8 R→R synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101366-C-T
10 A→A synonymous_variant gnomAD — 4.80e-06 — N/A 0.00 chr17-48101360-A-T
10 A→T missense_variant gnomAD — 3.60e-06 — N/A -1.54 chr17-48101362-C-T
12 F→F synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101354-G-A
13 L→L synonymous_variant gnomAD — 1.20e-05 — N/A 0.00 chr17-48101351-C-G
14 G→G synonymous_variant gnomAD — 2.40e-06 — N/A 0.00 chr17-48101348-G-A
14 G→G synonymous_variant gnomAD — 3.60e-06 — N/A 0.00 chr17-48101348-G-T
14 — frameshift_variant gnomAD — 2.40e-06 LoF — — chr17-48101348-GC-G
14 G→R missense_variant gnomAD — 1.20e-06 — N/A 0.33 chr17-48101350-C-G
15 A→D missense_variant gnomAD — 3.60e-06 — N/A -1.89 chr17-48101346-G-T
15 A→S missense_variant gnomAD — 6.00e-06 — N/A -0.78 chr17-48101347-C-A
15 A→T missense_variant gnomAD — 7.08e-05 — N/A -1.38 chr17-48101347-C-T
16 T→N missense_variant gnomAD — 1.20e-06 — N/A -1.50 chr17-48101343-G-T
17 P→P synonymous_variant gnomAD — 2.40e-06 — N/A 0.00 chr17-48101339-G-T
17 P→T missense_variant gnomAD — 1.20e-06 — N/A -1.14 chr17-48101341-G-T
18 P→S missense_variant gnomAD — 1.20e-06 — N/A -0.40 chr17-48101338-G-A
19 G→S missense_variant gnomAD — 1.20e-06 — N/A -0.02 chr17-48101335-C-T
21 P→P synonymous_variant gnomAD — 2.40e-06 — N/A 0.00 chr17-48101327-C-G
21 P→P synonymous_variant gnomAD — 4.80e-06 — N/A 0.00 chr17-48101327-C-T
21 P→Q missense_variant gnomAD — 2.40e-06 — N/A -1.05 chr17-48101328-G-T
22 — frameshift_variant gnomAD — 3.60e-06 LoF — — chr17-48101324-C-CGTCGG
22 T→P missense_variant gnomAD — 4.80e-06 — N/A 1.09 chr17-48101326-T-G
23 R→R synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101321-T-A
25 A→A synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101315-G-A
25 — frameshift_variant gnomAD — 1.20e-06 LoF — — chr17-48101316-G-GCGCGT
25 A→S missense_variant gnomAD — 7.19e-06 — N/A -0.03 chr17-48101317-C-A
25 — frameshift_variant gnomAD — 4.80e-06 LoF — — chr17-48101317-C-CA
26 S→S synonymous_variant gnomAD — 7.89e-01 — N/A 0.00 chr17-48101312-G-A
26 S→R missense_variant gnomAD — 4.08e-05 — N/A 0.30 chr17-48101312-G-C
26 S→T missense_variant gnomAD — 1.14e-04 — N/A -0.89 chr17-48101313-C-G
26 S→N missense_variant gnomAD — 1.20e-06 — N/A -2.08 chr17-48101313-C-T
27 S→S synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101309-G-A
27 S→N missense_variant gnomAD — 7.19e-06 — N/A -3.05 chr17-48101310-C-T
27 S→G missense_variant gnomAD — 1.20e-06 — N/A -0.14 chr17-48101311-T-C
28 A→A synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101306-T-C
28 A→V missense_variant gnomAD — 8.39e-05 — N/A -1.84 chr17-48101307-G-A
28 A→T missense_variant gnomAD — 2.40e-06 — N/A -1.86 chr17-48101308-C-T
29 A→V missense_variant gnomAD — 1.20e-06 — N/A -1.18 chr17-48101304-G-A
30 P→P synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101300-C-A
30 P→L missense_variant gnomAD — 2.04e-05 — N/A -0.42 chr17-48101301-G-A
30 P→R missense_variant gnomAD — 2.40e-06 — N/A 0.19 chr17-48101301-G-C
31 I→V missense_variant gnomAD — 1.20e-06 — N/A 1.39 chr17-48101299-T-C
32 P→L missense_variant gnomAD — 1.20e-06 — N/A -0.51 chr17-48101295-G-A
33 L→L synonymous_variant gnomAD — 9.59e-06 — N/A 0.00 chr17-48101291-G-A
33 L→F missense_variant gnomAD — 1.20e-06 — N/A -1.58 chr17-48101293-G-A
34 G→G synonymous_variant gnomAD — 2.40e-06 — N/A 0.00 chr17-48101288-C-A
34 G→E missense_variant gnomAD — 1.20e-06 — N/A -1.55 chr17-48101289-C-T
34 G→R missense_variant gnomAD — 1.20e-06 — N/A 0.92 chr17-48101290-C-G
35 L→L synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101285-G-A
35 L→L synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101285-G-C
35 L→F missense_variant gnomAD — 2.40e-06 — N/A -0.91 chr17-48101287-G-A
36 L→F missense_variant gnomAD — 7.19e-06 — N/A -1.34 chr17-48101282-C-G
37 G→G synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101279-G-A
38 A→S missense_variant gnomAD — 1.20e-06 — N/A -0.08 chr17-48101278-C-A
38 A→T missense_variant gnomAD — 1.20e-06 — N/A -1.48 chr17-48101278-C-T
40 L→L synonymous_variant gnomAD — 1.20e-06 — N/A 0.00 chr17-48101270-C-T
42 S→S synonymous_variant gnomAD — 4.57e-04 — N/A 0.00 chr17-48077038-G-A
42 S→S synonymous_variant COSMIC — — — N/A 0.00 COSV99848140
43 V→V synonymous_variant gnomAD — 6.91e-07 — N/A 0.00 chr17-48077035-G-C
43 V→I missense_variant gnomAD — 1.52e-05 — N/A -3.64 chr17-48077037-C-T
43 V→I missense_variant COSMIC — — — N/A -3.64 COSV99848059
44 T→T synonymous_variant gnomAD — 2.76e-06 — N/A 0.00 chr17-48077032-G-A
44 T→A missense_variant gnomAD — 6.91e-07 — N/A -3.11 chr17-48077034-T-C
44 — frameshift_variant gnomAD — 6.91e-07 LoF — — chr17-48077034-T-TCA
45 L→V missense_variant gnomAD — 6.91e-07 — N/A -5.76 chr17-48077031-G-C
46 — inframe_insertion gnomAD — 2.06e-06 — N/A — chr17-48077027-T-TAAA
47 T→S missense_variant gnomAD — 6.18e-06 — N/A -1.13 chr17-48077024-G-C
47 T→N missense_variant gnomAD — 6.87e-07 — N/A -4.07 chr17-48077024-G-T
50 L→L synonymous_variant gnomAD — 6.85e-07 — N/A 0.00 chr17-48077016-G-A
50 L→V missense_variant gnomAD — 2.19e-05 — N/A -6.18 chr17-48077016-G-C
51 A→A synonymous_variant gnomAD — 3.70e-05 — N/A 0.00 chr17-48077011-C-T
51 A→V missense_variant gnomAD — 6.85e-07 — N/A -5.70 chr17-48077012-G-A
51 A→V missense_variant COSMIC — — — N/A -5.70 COSV56682161
52 G→G synonymous_variant gnomAD — 6.85e-07 — N/A 0.00 chr17-48077008-G-A
52 G→G synonymous_variant COSMIC — — — N/A 0.00 COSV56681939
53 T→T synonymous_variant gnomAD — 6.85e-07 — N/A 0.00 chr17-48077005-A-G

90 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
54 M→I missense_variant gnomAD — 1.37e-06 damaging — -10.94 chr17-48077002-C-G
54 M→I missense_variant gnomAD — 6.85e-07 damaging — -10.94 chr17-48077002-C-T
54 M→T missense_variant gnomAD — 6.85e-07 damaging — -11.50 chr17-48077003-A-G
54 M→L missense_variant gnomAD — 6.85e-07 damaging — -11.19 chr17-48077004-T-G
54 M→V missense_variant COSMIC — — damaging — -11.44 COSV56682591
55 G→G synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr17-48076999-C-A
55 G→V missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.88) -9.25 chr17-48077000-C-A
55 G→W missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.97) -12.31 chr17-48077001-C-A
56 — frameshift_variant COSMIC — — LoF — — COSV56681712
56 — frameshift_variant COSMIC — — LoF — — COSV56681499
57 K→K synonymous_variant gnomAD — 2.74e-06 — — 0.00 chr17-48076993-T-C
58 Q→Q synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48076990-T-C
58 Q→K missense_variant COSMIC — — damaging ambiguous (0.37) -10.00 COSV56682149
59 N→K missense_variant gnomAD — 1.85e-05 damaging likely_pathogenic (0.68) -8.87 chr17-48076987-G-C
59 N→K missense_variant ClinVar Uncertain significance — damaging likely_pathogenic (0.68) -8.87 ClinVar:3827926
60 K→N missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.73) -9.94 chr17-48076984-C-G
60 — inframe_deletion gnomAD — 6.84e-07 — — — chr17-48076984-CTTG-C
60 K→Q missense_variant gnomAD — 1.37e-06 damaging likely_benign (0.24) -10.25 chr17-48076986-T-G
61 K→N missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.84) -9.87 chr17-48076981-C-A
61 K→R missense_variant gnomAD — 6.84e-07 damaging likely_benign (0.12) -9.06 chr17-48076982-T-C
62 K→N missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.58) -9.00 chr17-48076978-T-A
62 — inframe_deletion gnomAD — 1.37e-06 — — — chr17-48076978-TTTC-T
62 K→I missense_variant gnomAD — 6.84e-07 damaging ambiguous (0.56) -11.69 chr17-48076979-T-A
62 K→R missense_variant gnomAD — 9.58e-06 damaging likely_benign (0.12) -8.94 chr17-48076979-T-C
62 K→* stop_gained gnomAD — 6.84e-07 LoF — — chr17-48076980-T-A
62 K→E missense_variant gnomAD — 6.84e-07 damaging ambiguous (0.42) -9.69 chr17-48076980-T-C
63 V→V synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr17-48076975-C-T
63 V→G missense_variant gnomAD — 6.85e-07 damaging likely_benign (0.14) -8.75 chr17-48076976-A-C
63 V→M missense_variant gnomAD — 7.53e-06 damaging likely_benign (0.13) -8.37 chr17-48076977-C-T
63 V→L missense_variant COSMIC — — damaging likely_benign (0.20) -8.06 COSV56682280
66 V→V synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr17-48076966-C-T
66 V→L missense_variant gnomAD — 2.05e-06 damaging likely_benign (0.30) -7.78 chr17-48076968-C-A
66 V→M missense_variant gnomAD — 2.74e-06 damaging likely_benign (0.24) -8.68 chr17-48076968-C-T
67 L→L synonymous_variant gnomAD — 2.05e-06 — — 0.00 chr17-48076963-T-C
68 E→K missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.83) -11.12 chr17-48076962-C-T
69 E→Q missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.62) -9.69 chr17-48076959-C-G
69 E→K missense_variant COSMIC — — damaging likely_pathogenic (0.83) -9.56 COSV56681509
70 E→Q missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.61) -9.81 chr17-48076956-C-G
71 E→E synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr17-48076951-T-C
71 E→G missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.77) -9.56 chr17-48076952-T-C
72 E→Q missense_variant COSMIC — — damaging likely_pathogenic (0.95) -11.25 COSV99848313
73 E→E synonymous_variant gnomAD — 2.05e-06 — — 0.00 chr17-48076945-T-C
75 V→V synonymous_variant gnomAD — 2.74e-06 — — 0.00 chr17-48076939-C-T
75 V→V synonymous_variant COSMIC — — — — 0.00 COSV99848141
76 V→V synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48076936-C-A
76 V→V synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48076936-C-G
77 E→V missense_variant ClinVar — — damaging likely_pathogenic (1.00) -11.31 ClinVar:4423332
78 K→N missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.99) -9.37 chr17-48076930-T-A
80 L→L synonymous_variant gnomAD — 6.84e-06 — — 0.00 chr17-48076924-G-A
80 L→I missense_variant COSMIC — — damaging likely_benign (0.28) -9.56 COSV56682110
81 D→H missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.94) -7.89 chr17-48076923-C-G
81 D→N missense_variant gnomAD — 1.85e-05 damaging likely_pathogenic (0.56) -4.01 chr17-48076923-C-T
82 R→H missense_variant gnomAD — 2.74e-06 damaging likely_pathogenic (0.79) -7.03 chr17-48076919-C-T
82 R→C missense_variant gnomAD — 1.23e-05 damaging likely_pathogenic (0.87) -7.12 chr17-48076920-G-A
83 R→Q missense_variant gnomAD — 2.05e-06 damaging likely_pathogenic (0.99) -9.25 chr17-48076916-C-T
83 R→R synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48076917-G-T
83 R→R synonymous_variant COSMIC — — — — 0.00 COSV56682056
83 R→* stop_gained COSMIC — — LoF — — COSV56681749
84 V→V synonymous_variant gnomAD — 2.05e-06 — — 0.00 chr17-48076912-C-T
84 V→A missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.92) -7.43 chr17-48076913-A-G
85 V→V synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr17-48076909-T-C
85 V→L missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.76) -6.96 chr17-48076911-C-A
86 K→K synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48076906-C-T
87 G→G synonymous_variant gnomAD — 3.42e-06 — — 0.00 chr17-48076903-G-A
87 G→S missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.96) -7.97 chr17-48076905-C-T
87 G→S missense_variant COSMIC — — damaging likely_pathogenic (0.96) -7.97 COSV99847936
88 K→R missense_variant gnomAD — 2.05e-06 — likely_benign (0.09) -5.18 chr17-48076901-T-C
90 E→D missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (1.00) -7.72 chr17-48076894-C-G
90 E→K missense_variant COSMIC — — damaging likely_pathogenic (1.00) -10.19 COSV56682856
91 Y→Y synonymous_variant gnomAD — 1.71e-05 — — 0.00 chr17-48076891-G-A
92 L→L synonymous_variant gnomAD — 3.43e-06 — — 0.00 chr17-48076888-G-A
92 L→R missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.84) -9.56 chr17-48076889-A-C
92 L→F missense_variant COSMIC — — — ambiguous (0.35) -6.53 COSV56681814
93 L→L synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr17-48076885-T-G
94 K→K synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr17-48076882-C-T
94 K→E missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (1.00) -11.19 chr17-48076884-T-C
97 G→G synonymous_variant gnomAD — 4.39e-05 — — 0.00 chr17-48076873-T-C
98 F→F synonymous_variant gnomAD — 6.86e-07 — — 0.00 chr17-48076870-G-A
98 F→L missense_variant COSMIC — — damaging likely_pathogenic (1.00) -10.37 COSV56682209
101 E→K missense_variant gnomAD — 7.10e-07 damaging likely_pathogenic (0.84) -9.50 chr17-48076177-C-T
101 E→Q missense_variant ClinVar — — damaging likely_pathogenic (0.60) -11.12 ClinVar:4423331
101 E→Q missense_variant COSMIC — — damaging likely_pathogenic (0.60) -11.12 COSV56681530
102 D→H missense_variant gnomAD — 7.06e-07 damaging likely_pathogenic (0.97) -12.12 chr17-48076174-C-G
103 N→D missense_variant gnomAD — 1.41e-06 damaging likely_pathogenic (0.97) -10.37 chr17-48076171-T-C
103 N→S missense_variant COSMIC — — damaging likely_pathogenic (0.59) -9.00 COSV56681968
106 E→D missense_variant COSMIC — — damaging likely_pathogenic (1.00) -10.56 COSV99848274
108 E→D missense_variant COSMIC — — damaging likely_pathogenic (0.96) -8.69 COSV99848151
110 N→N synonymous_variant gnomAD — 1.38e-06 — — 0.00 chr17-48076148-G-A
111 L→L synonymous_variant gnomAD — 1.38e-06 — — 0.00 chr17-48076147-G-A
114 P→P synonymous_variant gnomAD — 1.51e-05 — — 0.00 chr17-48076136-G-A
114 P→P synonymous_variant gnomAD — 6.88e-07 — — 0.00 chr17-48076136-G-C
114 P→P synonymous_variant COSMIC — — — — 0.00 COSV99847948
115 D→N missense_variant COSMIC — — damaging likely_pathogenic (0.96) -8.31 COSV99847954
116 L→L synonymous_variant gnomAD — 1.23e-05 — — 0.00 chr17-48076130-G-A
118 A→A synonymous_variant gnomAD — 5.48e-06 — — 0.00 chr17-48076124-A-G
118 A→A synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr17-48076124-A-T
118 A→G missense_variant gnomAD — 1.37e-06 damaging ambiguous (0.38) -9.94 chr17-48076125-G-C
121 L→L synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr17-48076115-C-T
121 L→L synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr17-48076117-G-A
121 L→L synonymous_variant COSMIC — — — — 0.00 COSV105045650
122 Q→* stop_gained COSMIC — — LoF — — COSV99848158
123 S→L missense_variant gnomAD — 2.74e-06 damaging likely_benign (0.27) -9.37 chr17-48076110-G-A
123 S→L missense_variant ClinVar Uncertain significance — damaging likely_benign (0.27) -9.37 ClinVar:4648788
124 Q→R missense_variant gnomAD — 6.85e-07 — likely_benign (0.33) -7.47 chr17-48076107-T-C
124 Q→* stop_gained COSMIC — — LoF — — COSV99848270
125 K→R missense_variant gnomAD — 6.85e-07 — likely_benign (0.12) -6.44 chr17-48076104-T-C
125 K→Q missense_variant ClinVar Uncertain significance — damaging likely_benign (0.33) -8.75 ClinVar:4531663
126 T→A missense_variant gnomAD — 6.85e-07 — likely_benign (0.06) -6.06 chr17-48076102-T-C
128 H→P missense_variant gnomAD — 4.79e-06 — likely_benign (0.11) -7.21 chr17-48076095-T-G
130 T→R missense_variant gnomAD — 2.74e-06 damaging likely_benign (0.23) -7.90 chr17-48076089-G-C
131 D→G missense_variant gnomAD — 6.84e-07 — likely_benign (0.10) -6.27 chr17-48076086-T-C
131 D→N missense_variant gnomAD — 6.84e-07 — likely_benign (0.10) -6.15 chr17-48076087-C-T
131 D→G missense_variant ClinVar Uncertain significance — — likely_benign (0.10) -6.27 ClinVar:4220041
131 D→N missense_variant ClinVar Uncertain significance — — likely_benign (0.10) -6.15 ClinVar:4220044
132 K→K synonymous_variant gnomAD — 4.04e-05 — — 0.00 chr17-48076082-T-C
132 K→I missense_variant gnomAD — 6.84e-07 damaging ambiguous (0.43) -10.75 chr17-48076083-T-A
132 K→I missense_variant ClinVar Uncertain significance — damaging ambiguous (0.43) -10.75 ClinVar:4220042
133 S→S synonymous_variant gnomAD — 4.79e-06 — — 0.00 chr17-48076079-T-G
134 E→K missense_variant COSMIC — — damaging likely_benign (0.26) -8.68 COSV99848247
135 G→R missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.58) -8.76 chr17-48076075-C-G
135 G→R missense_variant COSMIC — — damaging likely_pathogenic (0.58) -8.76 COSV56682528
138 R→H missense_variant gnomAD — 7.53e-06 damaging likely_pathogenic (0.89) -9.31 chr17-48076065-C-T
138 R→C missense_variant gnomAD — 6.16e-06 damaging likely_pathogenic (0.96) -9.31 chr17-48076066-G-A
138 R→H missense_variant ClinVar Uncertain significance — damaging likely_pathogenic (0.89) -9.31 ClinVar:2290145
138 R→H missense_variant COSMIC — — damaging likely_pathogenic (0.89) -9.31 COSV56682901
138 R→C missense_variant COSMIC — — damaging likely_pathogenic (0.96) -9.31 COSV56682920
139 K→R missense_variant gnomAD — 8.90e-06 damaging likely_benign (0.11) -7.87 chr17-48076062-T-C
140 A→T missense_variant gnomAD — 1.37e-06 — likely_benign (0.08) -6.34 chr17-48076060-C-T
140 A→T missense_variant ClinVar Uncertain significance — — likely_benign (0.08) -6.34 ClinVar:4220043
141 D→G missense_variant gnomAD — 6.85e-07 damaging likely_benign (0.15) -8.36 chr17-48076056-T-C
142 S→A missense_variant gnomAD — 6.85e-07 damaging likely_benign (0.06) -9.87 chr17-48076054-A-C
142 S→T missense_variant gnomAD — 1.37e-06 — likely_benign (0.05) -7.31 chr17-48076054-A-T
146 D→V missense_variant gnomAD — 1.37e-06 damaging likely_benign (0.13) -9.56 chr17-48076041-T-A
146 D→V missense_variant ClinVar Uncertain significance — damaging likely_benign (0.13) -9.56 ClinVar:2307098
146 D→N missense_variant COSMIC — — damaging likely_benign (0.11) -7.93 COSV56682563
147 K→K synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr17-48076037-C-T
147 K→R missense_variant gnomAD — 2.05e-06 — likely_benign (0.09) -4.90 chr17-48076038-T-C
147 K→E missense_variant gnomAD — 6.85e-07 damaging likely_benign (0.18) -11.05 chr17-48076039-T-C
147 K→K synonymous_variant COSMIC — — — — 0.00 COSV56682520
147 K→N missense_variant COSMIC — — damaging likely_benign (0.29) -9.30 COSV99848170
148 G→G synonymous_variant gnomAD — 2.06e-06 — — 0.00 chr17-48076034-T-C
148 — frameshift_variant gnomAD — 1.37e-06 LoF — — chr17-48076035-CCCTT-C
148 G→R missense_variant gnomAD — 2.74e-06 damaging ambiguous (0.54) -7.55 chr17-48076036-C-T
149 E→E synonymous_variant gnomAD — 6.86e-07 — — 0.00 chr17-48076031-C-T
149 E→Q missense_variant COSMIC — — damaging likely_benign (0.23) -8.62 COSV99848203
150 E→D missense_variant gnomAD — 6.86e-07 — likely_benign (0.05) -5.84 chr17-48076028-C-G
151 S→S synonymous_variant gnomAD — 4.81e-06 — — 0.00 chr17-48076025-G-A
151 S→G missense_variant gnomAD — 6.86e-07 — likely_benign (0.06) -5.94 chr17-48076027-T-C
151 S→S synonymous_variant COSMIC — — — — 0.00 COSV99848275
153 P→P synonymous_variant gnomAD — 2.07e-06 — — 0.00 chr17-48076019-T-C
153 P→L missense_variant gnomAD — 1.38e-06 — likely_benign (0.09) -6.30 chr17-48076020-G-A
155 K→N missense_variant gnomAD — 6.90e-07 damaging likely_pathogenic (0.93) -10.37 chr17-48076013-C-A
155 K→K synonymous_variant gnomAD — 1.38e-06 — — 0.00 chr17-48076013-C-T
156 K→N missense_variant gnomAD — 6.91e-07 damaging likely_pathogenic (0.91) -10.25 chr17-48076010-C-G
156 K→R missense_variant gnomAD — 1.38e-06 — likely_benign (0.09) -5.37 chr17-48076011-T-C
156 K→N missense_variant COSMIC — — damaging likely_pathogenic (0.91) -10.25 COSV56681336
156 K→N missense_variant COSMIC — — damaging likely_pathogenic (0.91) -10.25 COSV99848297
157 — inframe_deletion gnomAD — 2.77e-06 — — — chr17-48076007-TTTC-T
157 K→R missense_variant gnomAD — 6.92e-07 — likely_benign (0.09) -6.75 chr17-48076008-T-C
158 E→G missense_variant gnomAD — 6.92e-07 damaging likely_benign (0.33) -8.81 chr17-48076005-T-C
159 E→V missense_variant gnomAD — 1.39e-06 damaging likely_benign (0.30) -8.24 chr17-48076002-T-A
159 E→Q missense_variant gnomAD — 6.94e-07 damaging ambiguous (0.43) -8.99 chr17-48076003-C-G
160 S→S synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr17-48075098-T-A
160 S→L missense_variant gnomAD — 6.85e-07 — likely_benign (0.08) -6.09 chr17-48075099-G-A
161 E→A missense_variant gnomAD — 6.85e-07 damaging ambiguous (0.50) -9.43 chr17-48075096-T-G
163 P→S missense_variant gnomAD — 6.84e-07 — ambiguous (0.53) -5.76 chr17-48075091-G-A
163 P→Q missense_variant COSMIC — — damaging likely_pathogenic (0.61) -7.20 COSV106082017
163 P→S missense_variant COSMIC — — — ambiguous (0.53) -5.76 COSV56682997
164 R→Q missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.92) -8.69 chr17-48075087-C-T
164 R→* stop_gained gnomAD — 2.05e-06 LoF — — chr17-48075088-G-A
164 R→* stop_gained COSMIC — — LoF — — COSV56682269
166 F→S missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (1.00) -10.44 chr17-48075081-A-G
167 A→A synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr17-48075077-A-C
167 A→A synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48075077-A-G
168 R→Q missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.99) -8.12 chr17-48075075-C-T
168 R→* stop_gained gnomAD — 6.84e-07 LoF — — chr17-48075076-G-A
168 R→R synonymous_variant COSMIC — — — — 0.00 COSV107309107
168 R→L missense_variant COSMIC — — damaging likely_pathogenic (1.00) -10.37 COSV99847942
168 R→Q missense_variant COSMIC — — damaging likely_pathogenic (0.99) -8.12 COSV56683114
168 R→* stop_gained COSMIC — — LoF — — COSV104387334
169 G→D missense_variant COSMIC — — damaging likely_pathogenic (0.89) -9.62 COSV105045685
171 E→K missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.87) -7.54 chr17-48075067-C-T
171 E→E synonymous_variant COSMIC — — — — 0.00 COSV56681442
172 P→P synonymous_variant gnomAD — 1.97e-04 — — 0.00 chr17-48075062-C-T
172 P→L missense_variant gnomAD — 7.52e-06 damaging likely_pathogenic (1.00) -10.81 chr17-48075063-G-A
172 P→P synonymous_variant COSMIC — — — — 0.00 COSV99848187
172 P→Q missense_variant COSMIC — — damaging likely_pathogenic (1.00) -12.12 COSV56682499
172 P→S missense_variant COSMIC — — damaging likely_pathogenic (1.00) -9.69 COSV99848079
173 E→D missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.92) -9.06 chr17-48075059-C-A
173 E→E synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr17-48075059-C-T
173 E→D missense_variant ClinVar Uncertain significance — damaging likely_pathogenic (0.92) -9.06 ClinVar:4648787
173 E→K missense_variant COSMIC — — damaging likely_pathogenic (1.00) -12.12 COSV56681862
174 R→R synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48075056-C-T
174 R→Q missense_variant COSMIC — — damaging likely_pathogenic (0.98) -7.87 COSV56682101
174 R→L missense_variant COSMIC — — damaging likely_pathogenic (0.99) -10.12 COSV99848174
175 I→V missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.96) -7.69 chr17-48075055-T-C
177 G→A missense_variant COSMIC — — damaging likely_pathogenic (1.00) -12.44 COSV56682437
179 T→T synonymous_variant gnomAD — 2.74e-06 — — 0.00 chr17-48075041-T-C
181 S→S synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48075035-G-A
182 S→S synonymous_variant COSMIC — — — — 0.00 COSV56681832
184 E→Q missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.92) -10.00 chr17-48075028-C-G
185 L→L synonymous_variant gnomAD — 9.59e-06 — — 0.00 chr17-48075023-G-A
186 M→L missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.91) -10.25 chr17-48075022-T-A
186 M→V missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.99) -11.50 chr17-48075022-T-C
186 — inframe_deletion COSMIC — — — — — COSV56681204
187 F→F synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr17-48075017-G-A
188 L→P missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (1.00) -13.06 chr17-48075015-A-G
188 L→L synonymous_variant COSMIC — — — — 0.00 COSV99848148
188 L→L synonymous_variant COSMIC — — — — 0.00 COSV56681918
189 M→I missense_variant gnomAD — 6.86e-07 damaging likely_pathogenic (0.97) -8.12 chr17-48075011-C-A
189 M→T missense_variant gnomAD — 6.86e-07 damaging likely_pathogenic (1.00) -11.81 chr17-48075012-A-G
190 K→K synonymous_variant gnomAD — 6.86e-07 — — 0.00 chr17-48075008-T-C
190 K→T missense_variant gnomAD — 6.86e-07 damaging likely_pathogenic (1.00) -11.87 chr17-48075009-T-G
192 K→R missense_variant gnomAD — 8.28e-06 — likely_benign (0.14) -6.94 chr17-48071577-T-C
193 N→K missense_variant COSMIC — — damaging likely_pathogenic (0.89) -8.94 COSV99848229
194 S→F missense_variant COSMIC — — damaging likely_pathogenic (0.99) -10.37 COSV56681364
197 A→A synonymous_variant gnomAD — 6.87e-07 — — 0.00 chr17-48071561-A-G
198 D→D synonymous_variant gnomAD — 6.87e-07 — — 0.00 chr17-48071558-G-A
200 V→L missense_variant gnomAD — 6.86e-07 damaging likely_pathogenic (1.00) -11.25 chr17-48071554-C-G
202 A→A synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr17-48071546-G-A
202 A→D missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (1.00) -12.00 chr17-48071547-G-T
202 A→V missense_variant COSMIC — — damaging likely_pathogenic (1.00) -10.62 COSV99848117
204 E→* stop_gained gnomAD — 6.85e-07 LoF — — chr17-48071542-C-A
204 E→K missense_variant COSMIC — — damaging likely_pathogenic (0.99) -10.94 COSV56681808
206 N→S missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.91) -12.44 chr17-48071535-T-C
207 V→F missense_variant gnomAD — 2.74e-06 damaging likely_pathogenic (0.57) -8.73 chr17-48071533-C-A
207 V→V synonymous_variant COSMIC — — — — 0.00 COSV56681933
208 K→K synonymous_variant COSMIC — — — — 0.00 COSV56682664
209 C→C synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr17-48071525-G-A
209 C→S missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (1.00) -5.97 chr17-48071526-C-G
210 P→L missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (1.00) -10.62 chr17-48071523-G-A
211 Q→Q synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48071519-C-T
211 Q→* stop_gained gnomAD — 6.84e-07 LoF — — chr17-48071521-G-A
212 V→F missense_variant gnomAD — 2.05e-06 damaging likely_pathogenic (0.99) -12.05 chr17-48071518-C-A
214 I→I synonymous_variant COSMIC — — — — 0.00 COSV56681722
214 I→T missense_variant COSMIC — — damaging likely_pathogenic (1.00) -11.06 COSV56682067
215 S→S synonymous_variant gnomAD — 2.05e-06 — — 0.00 chr17-48071507-G-T
216 F→F synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48071504-G-A
217 Y→Y synonymous_variant gnomAD — 1.37e-06 — — 0.00 chr17-48071501-A-G
217 Y→C missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (1.00) -11.94 chr17-48071502-T-C
220 R→K missense_variant COSMIC — — damaging likely_pathogenic (0.99) -11.06 COSV56682552
222 T→T synonymous_variant gnomAD — 4.11e-06 — — 0.00 chr17-48071486-C-T
222 T→K missense_variant COSMIC — — damaging likely_pathogenic (0.99) -13.94 COSV56681836
224 H→H synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48071480-A-G
225 S→S synonymous_variant gnomAD — 6.84e-07 — — 0.00 chr17-48071477-G-A
225 S→F missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.97) -11.12 chr17-48071478-G-A
225 S→A missense_variant gnomAD — 6.84e-07 damaging likely_benign (0.27) -9.06 chr17-48071479-A-C
225 S→P missense_variant gnomAD — 6.84e-07 damaging likely_pathogenic (0.98) -11.81 chr17-48071479-A-G
225 S→T missense_variant gnomAD — 6.84e-07 damaging ambiguous (0.44) -10.19 chr17-48071479-A-T
226 Y→Y synonymous_variant gnomAD — 2.94e-05 — — 0.00 chr17-48071474-G-A
226 Y→* stop_gained gnomAD — 6.85e-07 LoF — — chr17-48071474-G-T
227 P→S missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.58) -8.75 chr17-48071473-G-A
227 P→S missense_variant COSMIC — — damaging likely_pathogenic (0.58) -8.75 COSV108798400
228 S→S synonymous_variant gnomAD — 4.11e-06 — — 0.00 chr17-48071468-C-T
228 S→L missense_variant gnomAD — 2.05e-06 damaging likely_benign (0.21) -8.42 chr17-48071469-G-A
228 S→L missense_variant ClinVar Uncertain significance — damaging likely_benign (0.21) -8.42 ClinVar:3138046
228 S→S synonymous_variant COSMIC — — — — 0.00 COSV56681272
228 S→* stop_gained COSMIC — — LoF — — COSV99848014
229 E→K missense_variant COSMIC — — damaging likely_pathogenic (0.75) -12.00 COSV104555665
230 D→E missense_variant gnomAD — 4.80e-06 — likely_benign (0.09) -5.24 chr17-48071462-A-C
230 D→D synonymous_variant gnomAD — 6.85e-07 — — 0.00 chr17-48071462-A-G
230 D→Y missense_variant gnomAD — 6.85e-07 damaging likely_pathogenic (0.71) -11.56 chr17-48071464-C-A
230 D→N missense_variant gnomAD — 1.37e-06 damaging likely_benign (0.31) -10.18 chr17-48071464-C-T
230 D→E missense_variant ClinVar Uncertain significance — — likely_benign (0.09) -5.24 ClinVar:2517719
232 — inframe_deletion gnomAD — 2.06e-06 — — — chr17-48071456-GTCA-G
232 D→N missense_variant COSMIC — — damaging likely_benign (0.19) -8.62 COSV99848218
233 K→N missense_variant COSMIC — — damaging likely_pathogenic (0.72) -9.62 COSV99848111
233 — frameshift_variant COSMIC — — LoF — — COSV56682928
234 K→* stop_gained gnomAD — 6.85e-07 LoF — — chr17-48071452-T-A
235 D→V missense_variant gnomAD — 6.86e-07 damaging ambiguous (0.45) -9.47 chr17-48071448-T-A
235 — frameshift_variant gnomAD — 6.86e-07 LoF — — chr17-48071449-C-CT
235 — frameshift_variant gnomAD — 6.86e-07 LoF — — chr17-48071449-CTTTT-C
235 D→H missense_variant COSMIC — — damaging likely_pathogenic (0.73) -10.72 COSV56682228
235 D→Y missense_variant COSMIC — — damaging likely_pathogenic (0.65) -9.97 COSV56681987
236 — frameshift_variant gnomAD — 6.86e-07 LoF — — chr17-48071445-TC-T
236 D→Y missense_variant gnomAD — 1.37e-06 damaging likely_pathogenic (0.68) -10.43 chr17-48071446-C-A
236 D→N missense_variant gnomAD — 6.86e-07 — likely_benign (0.27) -7.43 chr17-48071446-C-T
236 — frameshift_variant gnomAD — 6.86e-07 LoF — — chr17-48071446-CA-C
238 N→K missense_variant gnomAD — 6.87e-07 damaging likely_pathogenic (0.68) -7.21 chr17-48071438-G-C
238 — frameshift_variant gnomAD — 1.37e-06 LoF — — chr17-48071439-TTCTTG-T
238 N→K missense_variant COSMIC — — damaging likely_pathogenic (0.68) -7.21 COSV56682095

281 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.

Evidence