SCN5A Variant L1704H
Summary of observed carriers, functional annotations, and structural context for SCN5A L1704H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/11 effective observations
Estimated BrS1 penetrance
18%
2/11 effective observations
Total carriers
1
0 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -6.48 | 1 | -6.08 | 0.99 | 17 | 1 |
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 |
|---|---|---|---|---|---|---|---|
| 26746457 | 2016 | 1 | 0 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 1 | 0 | 0 | – | |
| Variant features alone | – | 15 | 13 | 0 | 2 | – | – |
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) |
|---|---|---|---|---|---|---|
| 26746457 | 2016 |
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 | 7 | |
| 387 | 14 | |
| 1757 | 14 | |
| 1715 | 13 | |
| 1687 | 13 | |
| 391 | 15 | |
| 1698 | 10 | A1698T, |
| 1756 | 11 | I1756V, |
| 1673 | 11 | |
| 1675 | 10 | |
| 1764 | 13 | c.5290delG, V1764F |
| 1666 | 11 | |
| 371 | 15 | Q371E, |
| 1711 | 10 | c.5131delG, |
| 1754 | 12 | |
| 1707 | 5 | |
| 1694 | 8 | |
| 1704 | 0 | L1704H, |
| 1706 | 7 | Q1706H, Q1706H, |
| 1695 | 14 | Q1695X, |
| 1716 | 10 | p.L1716SfsX71, |
| 1714 | 15 | D1714G, |
| 1688 | 13 | |
| 1669 | 10 | |
| 1671 | 8 | |
| 1668 | 5 | M1668T, |
| 1676 | 11 | M1676T, M1676I, M1676I, M1676I, |
| 1692 | 10 | |
| 1753 | 14 | T1753A, |
| 1672 | 7 | S1672Y, |
| 1693 | 11 | |
| 378 | 11 | |
| 1699 | 9 | |
| 1665 | 10 | |
| 1712 | 11 | G1712S, G1712C, |
| 379 | 13 | |
| 1703 | 5 | |
| 1663 | 13 | |
| 397 | 14 | I397V, I397F, I397T, |
| 1759 | 10 | S1759C, |
| 1719 | 15 | |
| 1709 | 9 | p.T1709del, T1709R, T1709M, |
| 1701 | 6 | M1701I, M1701I, M1701I, |
| 1758 | 12 | I1758V, p.I1758del, |
| 1678 | 14 | N1678S, |
| 1223 | 14 | c.3667delG, |
| 1755 | 7 | |
| 1697 | 11 | |
| 393 | 14 | |
| 1674 | 12 | F1674V, |
| 1713 | 10 | |
| 390 | 11 | |
| 394 | 12 | |
| 1748 | 13 | p.G1748del, G1748D, |
| 1708 | 6 | T1708I, |
| 382 | 14 | |
| 1696 | 12 | |
| 374 | 12 | W374G, |
| 1705 | 5 | |
| 1700 | 6 | |
| 1717 | 13 | L1717P, |
| 1763 | 13 | V1763M, V1763L, V1763L, |
| 1751 | 9 | |
| 1677 | 14 | |
| 1760 | 13 | |
| 1752 | 9 | |
| 1670 | 10 | |
| 1661 | 13 | G1661R, G1661R, G1661E, |
| 375 | 12 | |
| 1691 | 13 | |
| 1710 | 11 | S1710L, |
| 1720 | 14 | c.5157delC, |
| 1679 | 11 | |
| 398 | 14 | |
| 1667 | 9 | V1667I, |
| 1664 | 10 |