SCN5A Variant c.4396_4397insG
Summary of observed carriers, functional annotations, and structural context for SCN5A c.4396_4397insG. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
5%
0/12 effective observations
Estimated BrS1 penetrance
54%
6/12 effective observations
Total carriers
2
2 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 65 | 6 |
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 |
|---|---|---|---|---|---|---|---|
| 17420262 | 2007 | 2 | 0 | 2 | 0 | ||
| Literature, cohort, and gnomAD | – | 2 | 0 | 0 | 2 | – | |
| Variant features alone | – | 15 | 11 | 0 | 4 | – | – |
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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 17420262 | 2007 |
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 |
|---|---|---|
| 939 | 8 | L939F, |
| 937 | 12 | |
| 1417 | 15 | |
| 1773 | 11 | |
| 1765 | 5 | |
| 943 | 13 | S943N, |
| 1457 | 13 | |
| 1757 | 13 | |
| 1472 | 10 | p.N1472del, N1472S, |
| 1771 | 11 | I1771T, |
| 1756 | 15 | I1756V, |
| 1461 | 11 | T1461S, T1461S, |
| 1764 | 9 | c.5290delG, V1764F, |
| 409 | 10 | L409V, L409P, |
| 1333 | 12 | |
| 934 | 11 | |
| 1458 | 12 | S1458Y, |
| 933 | 13 | |
| 1471 | 9 | |
| 935 | 7 | L935P, |
| 412 | 14 | V412D, |
| 1762 | 9 | p.I1762del, I1762M, |
| 1470 | 6 | |
| 1464 | 7 | c.4389_4396delCCTCTTTA, L1464P, |
| 927 | 15 | N927S, N927K, N927K, |
| 1466 | 0 | c.4396_4397insG, |
| 1776 | 15 | |
| 944 | 14 | |
| 1767 | 11 | Y1767C, |
| 1660 | 14 | I1660V, I1660S, |
| 1329 | 14 | G1329S, |
| 1769 | 7 | |
| 402 | 13 | F402L, F402L, F402L, |
| 1766 | 9 | M1766L, M1766V, M1766L, M1766T, |
| 1768 | 6 | I1768V, |
| 940 | 13 | S940N, |
| 1473 | 10 | F1473S, F1473C, |
| 1334 | 11 | I1334V, |
| 1341 | 14 | |
| 1468 | 6 | V1468F, V1468A, |
| 405 | 13 | |
| 1462 | 9 | |
| 938 | 9 | |
| 1474 | 13 | |
| 1759 | 13 | S1759C, |
| 1327 | 13 | |
| 942 | 11 | |
| 1758 | 14 | I1758V, p.I1758del, |
| 1459 | 13 | c.4376_4379delTCTT, |
| 1330 | 11 | A1330T, A1330P, A1330D, |
| 1772 | 9 | L1772V |
| 1460 | 11 | F1460L, F1460L, F1460L, |
| 1323 | 15 | V1323G, |
| 1338 | 14 | L1338V, |
| 410 | 12 | A410V, |
| 1770 | 11 | I1770V, |
| 413 | 12 | A413T, A413E, |
| 408 | 14 | |
| 941 | 13 | S941N, S941F, |
| 407 | 15 | |
| 1337 | 11 | |
| 1326 | 13 | A1326S, |
| 936 | 10 | |
| 1763 | 11 | V1763M, V1763L, V1763L, |
| 1465 | 6 | p.F1465_L1480dup, |
| 1760 | 10 | |
| 1467 | 4 | |
| 1331 | 14 | I1331V, |
| 1761 | 9 | c.5280delG, L1761F, L1761H, |
| 1469 | 5 | I1469V, |
| 406 | 10 | N406S, N406K, N406K, |
| 1336 | 15 | |
| 932 | 10 | |
| 931 | 13 | |
| 1463 | 6 | N1463Y, |