SCN5A Variant G1329S
Summary of observed carriers, functional annotations, and structural context for SCN5A G1329S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
44%
5/17 effective observations
Estimated BrS1 penetrance
9%
1/17 effective observations
Total carriers
7
0 BrS1 · 3 LQT3 · 4 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 (%) |
|---|---|---|---|---|---|
| -5.84 | 1 | 1.66 | 0.878 | 13 | 55 |
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 |
|---|---|---|---|---|---|---|---|
| 21216356 | 2011 | 1 | 1 | 0 | 0 | ||
| 24667783 | 2015 | 4 | 2 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 7 | 4 | 3 | 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 | 4 | V1328M, |
| 1271 | 14 | W1271C, W1271C, |
| 1480 | 15 | c.4437+5G>A, c.4438-1C>T, |
| 1765 | 14 | |
| 1757 | 14 | |
| 1472 | 7 | p.N1472del, N1472S, |
| 1315 | 14 | |
| 1320 | 14 | M1320I, M1320I, M1320I, |
| 1333 | 7 | |
| 1270 | 14 | A1270S, |
| 1477 | 14 | K1477N, K1477N, |
| 1471 | 11 | |
| 1762 | 11 | p.I1762del, I1762M, |
| 1470 | 13 | |
| 1466 | 14 | c.4396_4397insG, |
| 1478 | 15 | K1478E, |
| 944 | 14 | |
| 1329 | 0 | G1329S, |
| 1769 | 14 | |
| 1766 | 11 | M1766L, M1766V, M1766L, M1766T |
| 1479 | 11 | |
| 1473 | 10 | F1473S, F1473C, |
| 1334 | 8 | I1334V, |
| 1468 | 10 | V1468F, V1468A, |
| 1474 | 13 | |
| 1324 | 9 | |
| 1327 | 6 | |
| 1758 | 13 | I1758V, p.I1758del, |
| 1330 | 3 | A1330T, A1330P, A1330D, |
| 1321 | 15 | R1321K, |
| 1323 | 10 | V1323G, |
| 1338 | 14 | L1338V, |
| 1322 | 11 | c.3963+2T>C, c.3963+4A>G, |
| 1337 | 13 | |
| 1326 | 5 | A1326S, |
| 1763 | 13 | V1763M, V1763L, V1763L, |
| 1332 | 5 | P1332Q, P1332L, |
| 1465 | 13 | p.F1465_L1480dup, |
| 1467 | 13 | |
| 1476 | 9 | Q1476X, Q1476R, |
| 1331 | 5 | I1331V, |
| 1761 | 15 | c.5280delG, L1761F, L1761H, |
| 1475 | 11 | p.Q1475NfsX6, Q1475L, |
| 1469 | 9 | I1469V, |
| 1336 | 12 | |
| 1325 | 7 | N1325S, |
| 1335 | 10 | M1335R, |