SCN5A Variant L1761H
Summary of observed carriers, functional annotations, and structural context for SCN5A L1761H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
61%
4/12 effective observations
Estimated BrS1 penetrance
20%
2/12 effective observations
Total carriers
2
0 BrS1 · 2 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -6.47 | 1 | -4.22 | 0.989 | 26 | 61 |
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 |
|---|---|---|---|---|---|---|---|
| 20197117 | 2010 | 2 | 1 | 0 | 1 | AV block | |
| 19716085 | 2009 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 2 | 0 | 2 | 0 | – | |
| Variant features alone | – | 15 | 11 | 2 | 2 | – | – |
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.
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 |
|---|---|---|
| 1417 | 9 | |
| 1765 | 6 | |
| 1340 | 14 | V1340I, |
| 1457 | 12 | |
| 1757 | 5 | |
| 1413 | 11 | |
| 1472 | 14 | N1472S, p.N1472del, |
| 1339 | 15 | p.L1339del, L1339F, |
| 1756 | 6 | I1756V, |
| 1461 | 10 | T1461S, T1461S, |
| 1764 | 8 | V1764F, c.5290delG, |
| 371 | 15 | Q371E, |
| 1333 | 12 | |
| 1711 | 14 | c.5131delG, |
| 1754 | 10 | |
| 1707 | 12 | |
| 1458 | 11 | S1458Y, |
| 1671 | 14 | |
| 935 | 14 | L935P, |
| 1762 | 5 | p.I1762del, I1762M, |
| 1470 | 13 | |
| 1464 | 10 | c.4389_4396delCCTCTTTA, L1464P, |
| 1466 | 9 | c.4396_4397insG, |
| 1753 | 10 | T1753A, |
| 1767 | 13 | Y1767C, |
| 1660 | 14 | I1660V, I1660S, |
| 1329 | 15 | G1329S, |
| 1769 | 13 | |
| 1418 | 13 | |
| 402 | 14 | F402L, F402L, F402L, |
| 1766 | 10 | M1766L, M1766T, M1766V, M1766L, |
| 1768 | 11 | I1768V, |
| 1473 | 15 | F1473S, F1473C, |
| 1334 | 9 | I1334V, |
| 1341 | 11 | |
| 1468 | 11 | V1468F, V1468A, |
| 1663 | 14 | |
| 1462 | 7 | |
| 938 | 15 | |
| 1759 | 7 | S1759C, |
| 1327 | 12 | |
| 1709 | 11 | T1709M, T1709R, p.T1709del, |
| 1758 | 7 | I1758V, p.I1758del, |
| 1459 | 14 | c.4376_4379delTCTT, |
| 1755 | 9 | |
| 1330 | 12 | A1330P, A1330D, A1330T, |
| 1460 | 14 | F1460L, F1460L, F1460L, |
| 1713 | 11 | |
| 1338 | 9 | L1338V, |
| 1708 | 11 | T1708I, |
| 1409 | 14 | Y1409C, Y1409X, |
| 1345 | 12 | W1345C, W1345C, |
| 1337 | 10 | |
| 1342 | 14 | |
| 1326 | 14 | A1326S, |
| 1763 | 8 | V1763L, V1763L, V1763M, |
| 1751 | 15 | |
| 1416 | 11 | c.4245+1G>C, c.4245+2T>A, A1416E, c.4245+1G>A, A1416G, |
| 1332 | 14 | P1332L, P1332Q, |
| 1465 | 5 | p.F1465_L1480dup, |
| 1760 | 4 | |
| 1467 | 11 | |
| 1752 | 13 | |
| 1331 | 11 | I1331V, |
| 1761 | 0 | L1761H, L1761F, c.5280delG, |
| 1469 | 9 | I1469V, |
| 1336 | 14 | |
| 1710 | 10 | S1710L, |
| 1415 | 15 | |
| 1335 | 13 | M1335R, |
| 1419 | 14 | K1419E, |
| 1667 | 13 | V1667I, |
| 1414 | 13 | Q1414H, Q1414H, |
| 1664 | 13 | |
| 1463 | 9 | N1463Y, |