SCN5A Variant c.3963+2T>C
Summary of observed carriers, functional annotations, and structural context for SCN5A c.3963+2T>C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
0/13 effective observations
Estimated BrS1 penetrance
50%
6/13 effective observations
Total carriers
3
2 BrS1 · 0 LQT3 · 1 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 | 66 | 5 |
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 |
|---|---|---|---|---|---|---|---|
| 10471492 | 1999 | 15 | 0 | 0 | 15 | PCCD | |
| 16643399 | 2006 | 1 | 0 | 1 | 0 | ||
| 20031634 | 2009 | 9 | 0 | 2 | 6 | PCCD | |
| 22717692 | 2012 | 20 | 0 | 0 | 20 | Conduction defects | |
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 1 | 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.
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, |
| 1659 | 9 | |
| 1480 | 7 | c.4437+5G>A, c.4438-1C>T, |
| 1773 | 12 | |
| 1653 | 12 | |
| 1472 | 11 | p.N1472del, N1472S, |
| 1315 | 9 | |
| 1771 | 14 | I1771T, |
| 1652 | 14 | M1652T, M1652R, |
| 1314 | 11 | c.3940_3941delCT, |
| 1320 | 6 | M1320I, M1320I, M1320I, |
| 1656 | 8 | |
| 1477 | 7 | K1477N, K1477N, |
| 1471 | 14 | |
| 1762 | 14 | p.I1762del, I1762M, |
| 1470 | 13 | |
| 1478 | 12 | K1478E, |
| 1767 | 13 | Y1767C, |
| 1313 | 14 | |
| 1660 | 10 | I1660V, I1660S, |
| 1654 | 14 | |
| 1329 | 11 | G1329S, |
| 1769 | 11 | |
| 1316 | 13 | R1316Q, R1316L, |
| 1766 | 10 | M1766L, M1766V, M1766L, M1766T, |
| 1319 | 5 | G1319V, |
| 1768 | 15 | I1768V, |
| 1774 | 12 | N1774D, c.5321_5324dupACTT |
| 1479 | 9 | |
| 1473 | 7 | F1473S, F1473C, |
| 1663 | 12 | |
| 1657 | 11 | |
| 1474 | 11 | |
| 1662 | 13 | |
| 1324 | 6 | |
| 1481 | 11 | G1481R, G1481R, G1481E, G1481V, |
| 1317 | 10 | F1317C, |
| 1327 | 9 | |
| 1318 | 8 | |
| 1330 | 12 | A1330T, A1330P, A1330D, |
| 1321 | 7 | R1321K, |
| 1323 | 4 | V1323G, |
| 1770 | 9 | I1770V, |
| 1482 | 13 | |
| 1322 | 0 | c.3963+2T>C, c.3963+4A>G, |
| 1312 | 13 | |
| 1326 | 7 | A1326S, |
| 1763 | 13 | V1763M, V1763L, V1763L, |
| 1311 | 15 | L1311P, |
| 1476 | 5 | Q1476X, Q1476R, |
| 1661 | 13 | G1661R, G1661R, G1661E, |
| 1331 | 15 | I1331V, |
| 1655 | 11 | |
| 1475 | 11 | p.Q1475NfsX6, Q1475L, |
| 1469 | 12 | I1469V, |
| 1325 | 6 | N1325S, |
| 1658 | 13 |