SCN5A Variant V1667I
Summary of observed carriers, functional annotations, and structural context for SCN5A V1667I. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
24%
4/25 effective observations
Estimated BrS1 penetrance
8%
1/25 effective observations
Total carriers
15
1 BrS1 · 4 LQT3 · 10 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -0.96 | 0.986 | 3.12 | 0.802 | 10 | 19 |
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 |
|---|---|---|---|---|---|---|---|
| 11274952 | 2001 | 11 | 2 | 0 | 0 | ||
| 15840476 | 2005 | 1 | 1 | 0 | 0 | ||
| 15996170 | 2005 | 1 | 0 | 0 | 1 | VT | |
| 19843921 | 2009 | 1 | 0 | 1 | 0 | ||
| 20566482 | 2010 | 4 | 4 | 0 | 0 | ||
| 20659946 | 2010 | 7 | 7 | 0 | 0 | ||
| 27566755 | 2016 | 2 | 2 | 0 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 15 | 10 | 4 | 1 | – | |
| Variant features alone | – | 15 | 15 | 0 | 0 | – | – |
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 |
|---|---|---|
| 1702 | 14 | |
| 1328 | 15 | V1328M, |
| 1659 | 13 | |
| 1765 | 14 | |
| 1304 | 13 | T1304M, |
| 1757 | 12 | |
| 1315 | 14 | |
| 1216 | 15 | L1216V, |
| 1698 | 15 | A1698T, |
| 1756 | 12 | I1756V, |
| 1314 | 11 | c.3940_3941delCT, |
| 1320 | 13 | M1320I, M1320I, M1320I, |
| 1673 | 11 | |
| 1675 | 12 | |
| 1764 | 12 | V1764F, c.5290delG, |
| 1666 | 5 | |
| 1754 | 10 | |
| 1707 | 11 | |
| 1694 | 15 | |
| 1704 | 9 | L1704H, |
| 1706 | 14 | Q1706H, Q1706H, |
| 1669 | 7 | |
| 1671 | 6 | |
| 1762 | 11 | I1762M, p.I1762del, |
| 1668 | 5 | M1668T, |
| 1676 | 14 | M1676T, M1676I, M1676I, M1676I, |
| 1219 | 14 | S1219N, |
| 1753 | 14 | T1753A, |
| 1672 | 9 | S1672Y, |
| 1767 | 14 | Y1767C, |
| 1313 | 14 | |
| 1660 | 10 | I1660S, I1660V, |
| 1310 | 11 | |
| 1766 | 12 | M1766L, M1766T, M1766V, M1766L, |
| 1665 | 7 | |
| 1305 | 14 | |
| 1703 | 13 | |
| 1663 | 6 | |
| 1759 | 8 | S1759C, |
| 1662 | 10 | |
| 1324 | 13 | |
| 1327 | 12 | |
| 1709 | 13 | T1709M, p.T1709del, T1709R, |
| 1701 | 10 | M1701I, M1701I, M1701I, |
| 1307 | 10 | |
| 1758 | 7 | p.I1758del, I1758V, |
| 1223 | 14 | c.3667delG, |
| 1755 | 7 | |
| 1697 | 14 | |
| 1674 | 11 | F1674V, |
| 1713 | 15 | |
| 1323 | 13 | V1323G, |
| 394 | 15 | |
| 1708 | 9 | T1708I, |
| 1705 | 11 | |
| 1700 | 12 | |
| 1763 | 9 | V1763M, V1763L, V1763L, |
| 1751 | 11 | |
| 1311 | 9 | L1311P, |
| 1308 | 10 | L1308F, |
| 1760 | 13 | |
| 1752 | 13 | |
| 1670 | 5 | |
| 1661 | 9 | G1661R, G1661E, G1661R, |
| 1761 | 13 | L1761H, L1761F, c.5280delG, |
| 1710 | 15 | S1710L, |
| 398 | 14 | |
| 1667 | 0 | V1667I, |
| 1664 | 6 |