SCN5A Variant V1763L

Summary of observed carriers, functional annotations, and structural context for SCN5A V1763L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

62%

3/11 effective observations

Estimated BrS1 penetrance

13%

1/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

V1763L has not been reported 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 (%)
-2.77 0.974 2.9 0.929 17 71

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
30059973 2018 1 1 0 0
Literature, cohort, and gnomAD 1 0 1 0
Variant features alone 15 12 2 1

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

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
30059973 2018

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 V1763L.
Neighbour residue Distance (Å) Observed variants
403 14
1328 12 V1328M,
1659 11
1765 6
1653 15
1757 9
1472 13 p.N1472del, N1472S,
1315 14
1771 13 I1771T,
401 14 S401P,
1756 11 I1756V,
1314 13 c.3940_3941delCT,
1320 11 M1320I,
1764 4 V1764F, c.5290delG,
1666 11
371 15 Q371E,
1333 15
1754 12
1707 13
1656 12
1704 13 L1704H,
1671 13
1762 5 p.I1762del, I1762M,
1470 13
1668 11 M1668T,
1466 11 c.4396_4397insG,
1753 15 T1753A,
1767 8 Y1767C,
1660 6 I1660V, I1660S,
1329 13 G1329S,
1769 10
402 10 F402L,
1766 4 M1766T, M1766L, M1766V,
1319 14 G1319V,
1665 13
1768 9 I1768V,
1473 11 F1473S, F1473C,
1334 12 I1334V,
1468 13 V1468A, V1468F,
1663 7
397 14 I397F, I397T, I397V
1462 14
1657 10
1759 5 S1759C,
1662 11
1324 11
1327 8
1709 11 T1709R, T1709M, p.T1709del,
1758 6 p.I1758del, I1758V,
1755 9
1330 11 A1330P, A1330T, A1330D,
1772 14 L1772V,
1713 15
1323 9 V1323G,
1770 11 I1770V,
1708 9 T1708I,
1705 14
1322 13 c.3963+2T>C, c.3963+4A>G,
1326 10 A1326S,
1763 0 V1763M, V1763L,
1311 14 L1311P,
1465 11 p.F1465_L1480dup,
1760 8
1467 13
1670 14
1661 9 G1661R, G1661E,
1331 12 I1331V,
1761 8 L1761H, L1761F, c.5280delG,
1469 9 I1469V,
406 13 N406S, N406K,
1710 13 S1710L,
1325 14 N1325S,
398 12
1667 9 V1667I,
1664 6
1463 15 N1463Y,
1658 13