SCN5A Variant Q1491H
Summary of observed carriers, functional annotations, and structural context for SCN5A Q1491H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
50%
2/11 effective observations
Estimated BrS1 penetrance
10%
1/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -4.69 | 0.999 | -2.5 | 0.917 | 5 | 54 |
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 |
|---|---|---|---|---|---|---|---|
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 13 | 1 | 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 30059973 | 2018 |
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 |
|---|---|---|
| 1785 | 12 | |
| 1879 | 14 | |
| 1486 | 6 | p.F1486del, F1486L, F1486L, F1486L, |
| 1866 | 14 | |
| 1777 | 14 | V1777M, V1777L, V1777L |
| 1485 | 9 | |
| 1487 | 10 | M1487K, M1487L, M1487L, |
| 1492 | 6 | |
| 1875 | 10 | p.M1875dup, M1875T, M1875K, |
| 1872 | 12 | K1872N, K1872N, |
| 1491 | 0 | Q1491H, Q1491H, |
| 1501 | 15 | L1501V, p.L1501_K1505del, |
| 1874 | 10 | |
| 1862 | 12 | |
| 1493 | 7 | K1493X, K1493R, p.K1493del, |
| 1858 | 15 | |
| 1873 | 14 | I1873V, |
| 1865 | 15 | |
| 1478 | 13 | K1478E, |
| 1786 | 14 | L1786R, L1786Q, c.5356_5357delCT, |
| 1495 | 7 | Y1495S, |
| 1878 | 14 | |
| 1496 | 9 | |
| 1481 | 13 | G1481R, G1481V, G1481E, G1481R, |
| 1781 | 12 | E1781D, E1781G, E1781D, |
| 1499 | 12 | |
| 1877 | 13 | E1877K, |
| 1488 | 6 | T1488R, |
| 1784 | 11 | E1784K, E1784X, |
| 1498 | 10 | M1498T, M1498R, M1498V, |
| 1780 | 13 | E1780G, |
| 1500 | 14 | p.K1500del, |
| 1859 | 14 | |
| 1869 | 11 | |
| 1876 | 10 | |
| 1482 | 11 | |
| 1868 | 11 | |
| 1783 | 14 | |
| 1484 | 12 | |
| 1497 | 10 | |
| 1490 | 6 | |
| 1483 | 9 | Q1483H, Q1483H, |
| 1494 | 6 | |
| 1489 | 8 | E1489D, E1489D, |