SCN5A Variant Y1767C
Summary of observed carriers, functional annotations, and structural context for SCN5A Y1767C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
84%
10/18 effective observations
Estimated BrS1 penetrance
7%
1/18 effective observations
Total carriers
8
0 BrS1 · 8 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 (%) |
|---|---|---|---|---|---|
| -8.31 | 0.995 | -3.05 | 0.982 | 9 | 73 |
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 |
|---|---|---|---|---|---|---|---|
| 21076026 | 2011 | 4 | 4 | 0 | 0 | ||
| 16414944 | 2005 | 1 | 1 | 0 | 0 | ||
| 27566755 | 2016 | 4 | 4 | 0 | 0 | ||
| 30059973 | 2018 | 2 | 2 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 8 | 0 | 8 | 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 |
|---|---|---|
| 403 | 7 | |
| 1659 | 10 | |
| 404 | 11 | L404V, L404Q, |
| 1773 | 12 | |
| 1765 | 8 | |
| 396 | 14 | V396L, V396A, |
| 1653 | 8 | |
| 1771 | 6 | I1771T, |
| 401 | 9 | S401P, |
| 1652 | 13 | M1652T, M1652R, |
| 1320 | 12 | M1320I, M1320I, M1320I, |
| 1764 | 6 | c.5290delG, V1764F, |
| 371 | 13 | Q371E, |
| 409 | 12 | L409V, L409P, |
| 1650 | 11 | L1650F, |
| 1656 | 8 | |
| 1477 | 14 | K1477N, K1477N, |
| 1762 | 11 | p.I1762del, I1762M, |
| 1470 | 12 | |
| 1668 | 15 | M1668T, |
| 1466 | 11 | c.4396_4397insG, |
| 369 | 14 | M369K, |
| 1767 | 0 | Y1767C, |
| 1660 | 6 | I1660V, I1660S, |
| 1654 | 10 | |
| 1769 | 7 | |
| 402 | 5 | F402L, F402L, F402L, |
| 1766 | 7 | M1766L, M1766V, M1766L, M1766T, |
| 1319 | 13 | G1319V, |
| 1665 | 14 | |
| 1649 | 13 | A1649V, |
| 1768 | 6 | I1768V, |
| 1774 | 11 | N1774D, c.5321_5324dupACTT, |
| 1473 | 11 | F1473S, F1473C, |
| 1663 | 10 | |
| 399 | 10 | |
| 397 | 11 | I397V, I397F, I397T, |
| 405 | 10 | |
| 1657 | 5 | |
| 1759 | 11 | S1759C, |
| 1662 | 11 | |
| 1324 | 14 | |
| 1327 | 14 | |
| 1709 | 12 | p.T1709del, T1709R, T1709M, |
| 1758 | 14 | I1758V, p.I1758del, |
| 1772 | 10 | L1772V, |
| 395 | 14 | |
| 1323 | 10 | V1323G, |
| 394 | 13 | |
| 410 | 13 | A410V, |
| 1770 | 6 | I1770V, |
| 1651 | 14 | |
| 1708 | 12 | T1708I, |
| 408 | 14 | |
| 1705 | 15 | |
| 1322 | 13 | c.3963+2T>C, c.3963+4A>G, |
| 407 | 12 | |
| 1326 | 13 | A1326S, |
| 1763 | 8 | V1763M, V1763L, V1763L, |
| 1760 | 12 | |
| 1467 | 15 | |
| 1775 | 14 | F1775V, p.F1775LfsX15 |
| 1661 | 8 | G1661R, G1661R, G1661E, |
| 1761 | 13 | c.5280delG, L1761F, L1761H, |
| 1655 | 10 | |
| 1469 | 11 | I1469V, |
| 406 | 8 | N406S, N406K, N406K, |
| 398 | 7 | |
| 400 | 10 | G400R, G400R, G400E, G400A, |
| 1667 | 14 | V1667I, |
| 1664 | 9 | |
| 1658 | 9 |