SCN5A Variant E1574K
Summary of observed carriers, functional annotations, and structural context for SCN5A E1574K. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/14 effective observations
Estimated BrS1 penetrance
67%
9/14 effective observations
Total carriers
4
4 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -3.61 | 0.981 | -2.88 | 0.958 | 86 | 0 |
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 |
|---|---|---|---|---|---|---|---|
| 19029124 | 2009 | 1 | 0 | 1 | 0 | ||
| 26941339 | 2016 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 4 | 0 | 4 | 0 | ||
| Literature, cohort, and gnomAD | – | 4 | 0 | 0 | 4 | – | |
| Variant features alone | – | 15 | 10 | 0 | 5 | – | – |
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 |
|---|---|---|
| 1569 | 9 | A1569P, |
| 1525 | 9 | V1525M, V1525A, |
| 1524 | 10 | I1524T, |
| 1586 | 9 | |
| 1567 | 11 | F1567L, F1567L, F1567L, |
| 1536 | 13 | |
| 1538 | 10 | |
| 1531 | 9 | |
| 1566 | 13 | |
| 1635 | 14 | |
| 1568 | 10 | |
| 1587 | 13 | F1587V, |
| 1602 | 13 | |
| 1534 | 6 | |
| 1601 | 15 | L1601H, |
| 1522 | 13 | |
| 1575 | 4 | C1575S, C1575S, |
| 1600 | 12 | |
| 1571 | 5 | F1571C, |
| 1523 | 15 | D1523N, |
| 1521 | 11 | I1521K, I1521T, |
| 1527 | 12 | K1527R, |
| 1572 | 6 | |
| 1570 | 7 | p.1570_F1571insI, I1570V, p.I1570dup, |
| 1529 | 12 | |
| 1599 | 9 | |
| 1526 | 13 | T1526P, |
| 1583 | 15 | R1583C, R1583H, |
| 1580 | 11 | |
| 1630 | 14 | I1630V, I1630R, |
| 1532 | 12 | V1532I, V1532F, |
| 1626 | 13 | R1626C, R1626H, R1626P, R1626L, |
| 1603 | 14 | I1603F, |
| 1625 | 14 | |
| 1576 | 7 | |
| 1596 | 10 | F1596I, F1596C, |
| 1628 | 14 | |
| 1589 | 12 | |
| 1632 | 10 | R1632C, R1632H, R1632L |
| 1539 | 14 | C1539Y, C1539F, |
| 1597 | 12 | V1597M, |
| 1530 | 7 | |
| 1573 | 5 | |
| 1535 | 9 | |
| 1537 | 9 | |
| 1594 | 13 | F1594S, |
| 1581 | 11 | A1581S, |
| 1591 | 13 | W1591X, |
| 1593 | 12 | I1593M, |
| 1595 | 7 | |
| 1629 | 9 | R1629G, R1629X, R1629Q, |
| 1574 | 0 | c.4719C>T, E1574K, |
| 1533 | 10 | T1533I, |
| 1541 | 13 | |
| 1592 | 8 | |
| 1578 | 5 | c.4732_4733dupAA, |
| 1540 | 14 | |
| 1528 | 15 | |
| 1631 | 15 | G1631D, |
| 1590 | 14 | |
| 1582 | 11 | L1582P, |
| 1579 | 9 | L1579fsX53, |
| 1598 | 10 | V1598A, |
| 1577 | 6 |