SCN5A Variant R1629Q
Summary of observed carriers, functional annotations, and structural context for SCN5A R1629Q. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/18 effective observations
Estimated BrS1 penetrance
41%
7/18 effective observations
Total carriers
8
4 BrS1 · 0 LQT3 · 4 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -3.7 | 1 | -2.7 | 0.963 | 51 | 10 |
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 |
|---|---|---|---|---|---|---|---|
| 24167619 | 2013 | 3 | 0 | 2 | 0 | ||
| 21273195 | 2011 | 2 | 0 | 2 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 8 | 4 | 0 | 4 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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 |
|---|---|---|
| 266 | 13 | L266H, |
| 1569 | 13 | A1569P, |
| 1544 | 14 | T1544P, |
| 1627 | 7 | |
| 1586 | 12 | |
| 1567 | 11 | F1567L, F1567L, F1567L, |
| 1624 | 10 | V1624I, |
| 1536 | 13 | |
| 1538 | 5 | |
| 1531 | 12 | |
| 1566 | 15 | |
| 1635 | 11 | |
| 1568 | 11 | |
| 1587 | 15 | F1587V, |
| 1634 | 13 | L1634P |
| 1543 | 14 | V1543L, V1543L, V1543A, |
| 1602 | 12 | |
| 1534 | 9 | |
| 1542 | 9 | |
| 1601 | 12 | L1601H, |
| 1575 | 11 | C1575S, C1575S, |
| 1600 | 13 | |
| 1571 | 8 | F1571C, |
| 1572 | 12 | |
| 1564 | 13 | |
| 1570 | 12 | p.1570_F1571insI, I1570V, p.I1570dup, |
| 1599 | 9 | |
| 1545 | 12 | |
| 1630 | 6 | I1630V, I1630R, |
| 1532 | 14 | V1532I, V1532F, |
| 1626 | 7 | R1626C, R1626H, R1626P, R1626L, |
| 267 | 14 | |
| 1625 | 7 | |
| 262 | 15 | S262G, |
| 1596 | 11 | F1596I, F1596C, |
| 1628 | 6 | |
| 1589 | 12 | |
| 1632 | 5 | R1632C, R1632H, R1632L, |
| 1539 | 9 | C1539Y, C1539F, |
| 1597 | 9 | V1597M, |
| 1530 | 13 | |
| 1573 | 13 | |
| 1535 | 8 | |
| 1537 | 9 | |
| 1594 | 7 | F1594S, |
| 259 | 13 | |
| 1633 | 10 | |
| 1591 | 7 | W1591X, |
| 1593 | 10 | I1593M, |
| 1595 | 5 | |
| 1636 | 13 | |
| 263 | 12 | V263I, |
| 1629 | 0 | R1629G, R1629X, R1629Q, |
| 1574 | 9 | c.4719C>T, E1574K, |
| 1533 | 13 | T1533I, |
| 1541 | 8 | |
| 1592 | 9 | |
| 1578 | 11 | c.4732_4733dupAA, |
| 1540 | 12 | |
| 1631 | 8 | G1631D, |
| 1590 | 10 | |
| 1622 | 11 | |
| 1621 | 14 | |
| 1598 | 7 | V1598A, |
| 1623 | 13 | c.4867delC, R1623X, R1623Q, R1623L, |