SCN5A Variant A1330D
Summary of observed carriers, functional annotations, and structural context for SCN5A A1330D. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
63%
3/11 effective observations
Estimated BrS1 penetrance
11%
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 (%) |
|---|---|---|---|---|---|
| -5.85 | 1 | -3.49 | 0.958 | 5 | 77 |
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 |
|---|---|---|---|---|---|---|---|
| 27566755 | 2016 | 1 | 1 | 0 | 0 | ||
| 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.
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 | 6 | V1328M, |
| 1765 | 12 | |
| 1757 | 11 | |
| 1472 | 6 | p.N1472del, N1472S, |
| 1339 | 15 | L1339F, p.L1339del, |
| 1320 | 15 | M1320I, M1320I, M1320I, |
| 1764 | 14 | c.5290delG, V1764F, |
| 1333 | 5 | |
| 1477 | 15 | K1477N, K1477N, |
| 1471 | 10 | |
| 1762 | 8 | p.I1762del, I1762M, |
| 1470 | 11 | |
| 1464 | 13 | c.4389_4396delCCTCTTTA, L1464P, |
| 1466 | 11 | c.4396_4397insG, |
| 944 | 13 | |
| 1660 | 15 | I1660V, I1660S, |
| 1329 | 3 | G1329S, |
| 1769 | 13 | |
| 1766 | 9 | M1766L, M1766V, M1766L, M1766T, |
| 1768 | 15 | I1768V, |
| 1479 | 13 | |
| 1473 | 9 | F1473S, F1473C, |
| 1334 | 5 | I1334V, |
| 1468 | 7 | V1468F, V1468A, |
| 1663 | 14 | |
| 1474 | 13 | |
| 1759 | 14 | S1759C, |
| 1324 | 10 | |
| 1327 | 6 | |
| 1758 | 11 | I1758V, p.I1758del, |
| 1330 | 0 | A1330T, A1330P, A1330D, |
| 1323 | 11 | V1323G, |
| 1338 | 11 | L1338V, |
| 1770 | 15 | I1770V |
| 1322 | 12 | c.3963+2T>C, c.3963+4A>G, |
| 1337 | 10 | |
| 1326 | 6 | A1326S, |
| 1763 | 11 | V1763M, V1763L, V1763L, |
| 1332 | 5 | P1332Q, P1332L, |
| 1465 | 10 | p.F1465_L1480dup, |
| 1467 | 11 | |
| 1476 | 11 | Q1476X, Q1476R, |
| 1331 | 4 | I1331V, |
| 1761 | 12 | c.5280delG, L1761F, L1761H, |
| 1475 | 12 | p.Q1475NfsX6, Q1475L, |
| 1469 | 7 | I1469V, |
| 1336 | 10 | |
| 1325 | 9 | N1325S, |
| 1335 | 8 | M1335R, |