SCN5A Variant V1328M
Summary of observed carriers, functional annotations, and structural context for SCN5A V1328M. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
24%
1/11 effective observations
Estimated BrS1 penetrance
37%
4/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -1.96 | 0.988 | 3.37 | 0.775 | 50 | 35 |
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 |
|---|---|---|---|---|---|---|---|
| 27560382 | 2016 | 1 | 0 | 1 | 0 | drug induced BrS | |
| 28341781 | 2017 | 1 | 0 | 1 | 0 | ||
| 29574140 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 11 | 1 | 3 | – | – |
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 | 0 | V1328M, |
| 1271 | 10 | W1271C, W1271C, |
| 1757 | 14 | |
| 1472 | 10 | p.N1472del, N1472S, |
| 1315 | 11 | |
| 1274 | 15 | |
| 1314 | 13 | c.3940_3941delCT, |
| 1320 | 11 | M1320I, M1320I, M1320I, |
| 1333 | 10 | |
| 1270 | 11 | A1270S, |
| 1471 | 15 | |
| 1762 | 11 | p.I1762del, I1762M, |
| 1660 | 14 | I1660V, I1660S, |
| 1329 | 4 | G1329S, |
| 1766 | 11 | M1766L, M1766V, M1766L, M1766T |
| 1319 | 14 | G1319V, |
| 1479 | 13 | |
| 1473 | 11 | F1473S, F1473C, |
| 1334 | 10 | I1334V, |
| 1468 | 13 | V1468F, V1468A, |
| 1663 | 12 | |
| 1324 | 6 | |
| 1327 | 4 | |
| 1758 | 12 | I1758V, p.I1758del, |
| 1330 | 6 | A1330T, A1330P, A1330D, |
| 1321 | 12 | R1321K, |
| 1323 | 9 | V1323G, |
| 1322 | 10 | c.3963+2T>C, c.3963+4A>G, |
| 1312 | 12 | |
| 1326 | 6 | A1326S, |
| 1763 | 12 | V1763M, V1763L, V1763L, |
| 1311 | 12 | L1311P, |
| 1332 | 8 | P1332Q, P1332L, |
| 1465 | 15 | p.F1465_L1480dup, |
| 1476 | 10 | Q1476X, Q1476R, |
| 1331 | 6 | I1331V, |
| 1475 | 13 | p.Q1475NfsX6, Q1475L, |
| 1469 | 11 | I1469V, |
| 1336 | 14 | |
| 1269 | 13 | N1269S, |
| 1325 | 6 | N1325S, |
| 1335 | 11 | M1335R, |
| 1667 | 15 | V1667I, |