SCN5A Variant I1331V

Summary of observed carriers, functional annotations, and structural context for SCN5A I1331V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

30%

1/11 effective observations

Estimated BrS1 penetrance

8%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

I1331V is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-0.98 0.967 2.02 0.887 6 49

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 14 1 0 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near I1331V.
Neighbour residue Distance (Å) Observed variants
1328 6 V1328M,
1271 14 W1271C, W1271C,
1765 13
1340 15 V1340I,
1757 10
1472 10 p.N1472del, N1472S,
1339 13 L1339F, p.L1339del,
1756 15 I1756V,
1333 6
1754 13
1270 14 A1270S,
1471 14
1762 8 p.I1762del, I1762M,
1470 15
1464 14 c.4389_4396delCCTCTTTA, L1464P,
1466 14 c.4396_4397insG,
1329 5 G1329S,
1766 11 M1766L, M1766V, M1766L, M1766T
1473 13 F1473S, F1473C,
1334 5 I1334V,
1341 14
1468 10 V1468F, V1468A,
1663 14
1759 13 S1759C,
1324 11
1327 6
1758 10 I1758V, p.I1758del,
1330 4 A1330T, A1330P, A1330D,
1323 13 V1323G,
1338 10 L1338V,
1322 15 c.3963+2T>C, c.3963+4A>G,
1337 10
1326 9 A1326S,
1763 12 V1763M, V1763L, V1763L,
1311 15 L1311P,
1332 4 P1332Q, P1332L,
1465 11 p.F1465_L1480dup,
1467 14
1476 14 Q1476X, Q1476R,
1331 0 I1331V,
1761 11 c.5280delG, L1761F, L1761H,
1469 10 I1469V,
1336 9
1325 11 N1325S,
1335 6 M1335R,