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