SCN5A Variant I1762M

Summary of observed carriers, functional annotations, and structural context for SCN5A I1762M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

40%

2/12 effective observations

Estimated BrS1 penetrance

10%

1/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

I1762M is present in 2 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 2 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-2.4 1 0.06 0.742 13 75

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 – 2 2 0 0 –
Variant features alone – 15 12 2 1 – –

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 I1762M.
Neighbour residue Distance (Å) Observed variants
1328 11 V1328M,
1417 14
1765 6
1757 6
1472 11 p.N1472del, N1472S,
1756 9 I1756V,
1461 14 T1461S, T1461S,
1320 14 M1320I, M1320I, M1320I,
1764 7 c.5290delG, V1764F,
1666 14
1333 11
1754 11
1707 14
1471 14
1671 13
1762 0 I1762M, p.I1762del,
1470 12
1464 12 L1464P, c.4389_4396delCCTCTTTA,
1668 14 M1668T,
1466 9 c.4396_4397insG,
1753 13 T1753A,
1767 11 Y1767C,
1660 10 I1660V, I1660S,
1329 11 G1329S,
1769 11
402 14 F402L, F402L, F402L,
1766 6 M1766V, M1766T, M1766L, M1766L,
1768 10 I1768V,
1473 11 F1473C, F1473S,
1334 7 I1334V,
1341 14
1468 10 V1468F, V1468A,
1663 10
1657 14
1462 11
1759 6 S1759C,
1324 11
1327 7
1709 13 T1709M, T1709R, p.T1709del,
1758 5 I1758V, p.I1758del,
1755 10
1330 8 A1330P, A1330D, A1330T,
1713 14
1323 11 V1323G,
1338 11 L1338V,
1770 13 I1770V,
1708 11 T1708I,
1322 14 c.3963+2T>C, c.3963+4A>G,
1337 11
1326 10 A1326S,
1763 5 V1763M, V1763L, V1763L,
1332 12 P1332L, P1332Q,
1465 7 p.F1465_L1480dup,
1760 8
1467 11
1752 15
1661 13 G1661R, G1661R, G1661E,
1331 8 I1331V,
1761 5 c.5280delG, L1761H, L1761F,
1469 7 I1469V,
406 15 N406K, N406K, N406S,
1336 14
1710 13 S1710L,
1325 14 N1325S,
1335 12 M1335R,
1667 11 V1667I,
1664 11
1463 12 N1463Y,