SCN5A Variant I1334V
Summary of observed carriers, functional annotations, and structural context for SCN5A I1334V. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
51%
4/13 effective observations
Estimated BrS1 penetrance
9%
1/13 effective observations
Total carriers
3
0 BrS1 · 2 LQT3 · 1 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 (%) |
|---|---|---|---|---|---|
| -0.98 | 0.995 | 2.6 | 0.881 | 13 | 56 |
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 |
|---|---|---|---|---|---|---|---|
| 22677073 | 2012 | 1 | 0 | 0 | 1 | SUDS | |
| 23098067 | 2012 | 1 | 1 | 0 | 0 | ||
| 19716085 | 2009 | 1 | 1 | 0 | 0 | ||
| 30059973 | 2018 | 3 | 3 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 1 | 2 | 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.
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 |
|---|---|---|
| 1328 | 10 | V1328M, |
| 1765 | 11 | |
| 1340 | 10 | V1340I, |
| 1757 | 8 | |
| 1472 | 10 | p.N1472del, N1472S, |
| 1339 | 10 | L1339F, p.L1339del, |
| 1756 | 13 | I1756V, |
| 1461 | 12 | T1461S, T1461S, |
| 1764 | 14 | c.5290delG, V1764F, |
| 1333 | 4 | |
| 1754 | 13 | |
| 1471 | 12 | |
| 1762 | 7 | p.I1762del, I1762M, |
| 1470 | 13 | |
| 1464 | 10 | c.4389_4396delCCTCTTTA, L1464P, |
| 1466 | 11 | c.4396_4397insG, |
| 1753 | 14 | T1753A, |
| 944 | 14 | |
| 1329 | 8 | G1329S, |
| 1769 | 15 | |
| 1766 | 11 | M1766L, M1766V, M1766L, M1766T |
| 1334 | 0 | I1334V, |
| 1473 | 13 | F1473S, F1473C, |
| 1341 | 10 | |
| 1468 | 7 | V1468F, V1468A, |
| 1462 | 12 | |
| 1759 | 13 | S1759C, |
| 1324 | 14 | |
| 1327 | 9 | |
| 942 | 14 | |
| 1758 | 10 | I1758V, p.I1758del, |
| 1330 | 5 | A1330T, A1330P, A1330D, |
| 1460 | 14 | F1460L, F1460L, F1460L, |
| 1323 | 15 | V1323G, |
| 1338 | 6 | L1338V, |
| 1343 | 15 | |
| 1345 | 14 | W1345C, W1345C, |
| 1337 | 5 | |
| 1342 | 13 | |
| 1326 | 11 | A1326S, |
| 1763 | 12 | V1763M, V1763L, V1763L, |
| 1332 | 6 | P1332Q, P1332L, |
| 1465 | 6 | p.F1465_L1480dup, |
| 1760 | 13 | |
| 1467 | 10 | |
| 1331 | 5 | I1331V, |
| 1761 | 9 | c.5280delG, L1761F, L1761H, |
| 1469 | 8 | I1469V, |
| 1336 | 7 | |
| 824 | 13 | |
| 1325 | 14 | N1325S, |
| 1335 | 5 | M1335R, |
| 828 | 14 | L828V, |
| 1463 | 13 | N1463Y, |