SCN5A Variant c.4719C>T
Summary of observed carriers, functional annotations, and structural context for SCN5A c.4719C>T. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/12 effective observations
Estimated BrS1 penetrance
64%
7/12 effective observations
Total carriers
2
2 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 (%) |
---|---|---|---|---|---|
NA | NA | NA | None | 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 |
---|---|---|---|---|---|---|---|
21273195 | 2011 | 2 | 0 | 2 | 0 | ||
23425522 | 2013 | 2 | 0 | 2 | 0 | ||
27668095 | 2016 | 2 | 0 | 0 | 2 | first degree heart block | |
Literature, cohort, and gnomAD | – | 2 | 0 | 0 | 2 | – | |
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 | I1521T, I1521K, |
1527 | 12 | K1527R, |
1572 | 6 | |
1570 | 7 | p.I1570dup, p.1570_F1571insI, I1570V, |
1529 | 12 | |
1599 | 9 | |
1526 | 13 | T1526P, |
1583 | 15 | R1583C, R1583H, |
1580 | 11 | |
1630 | 14 | I1630R, I1630V, |
1532 | 12 | V1532I, V1532F, |
1626 | 13 | R1626P, R1626H, R1626L, R1626C, |
1603 | 14 | I1603F, |
1625 | 14 | |
1576 | 7 | |
1596 | 10 | F1596I, F1596C, |
1628 | 14 | |
1589 | 12 | |
1632 | 10 | R1632H, R1632C, R1632L, |
1539 | 14 | C1539F, C1539Y, |
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 |