SCN5A Variant A1649V
Summary of observed carriers, functional annotations, and structural context for SCN5A A1649V. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
44%
2/11 effective observations
Estimated BrS1 penetrance
49%
5/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -3.73 | 1 | -1.66 | 0.966 | 65 | 75 |
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 |
|---|---|---|---|---|---|---|---|
| 17081365 | 2006 | 1 | 0 | 1 | 0 | ||
| 20877689 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 9 | 2 | 4 | – | – |
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 |
|---|---|---|
| 403 | 10 | |
| 414 | 13 | M414V, |
| 1643 | 10 | I1643L, |
| 404 | 12 | L404V, L404Q, |
| 1778 | 7 | |
| 1773 | 10 | |
| 1653 | 6 | |
| 1771 | 8 | I1771T, |
| 1652 | 4 | M1652T, M1652R, |
| 1634 | 12 | L1634P, |
| 1777 | 8 | V1777L, V1777M, |
| 409 | 14 | L409V, L409P, |
| 1650 | 4 | L1650F, |
| 1656 | 11 | |
| 1641 | 13 | |
| 1477 | 13 | K1477N, |
| 1779 | 9 | T1779M, |
| 1776 | 9 | |
| 1787 | 11 | S1787N, |
| 1767 | 13 | Y1767C, |
| 1654 | 8 | |
| 1786 | 15 | c.5356_5357delCT, L1786Q, L1786R, |
| 1648 | 4 | |
| 1769 | 12 | |
| 1649 | 0 | A1649V, |
| 1768 | 14 | I1768V, |
| 1774 | 6 | N1774D, c.5321_5324dupACTT, |
| 1644 | 10 | R1644C, R1644L, R1644H, |
| 1640 | 14 | |
| 256 | 13 | |
| 399 | 14 | |
| 405 | 15 | |
| 1657 | 11 | |
| 1496 | 14 | |
| 1781 | 11 | E1781G, E1781D, |
| 1789 | 12 | |
| 1772 | 10 | L1772V, |
| 1645 | 7 | T1645M, |
| 410 | 11 | A410V, |
| 1780 | 13 | E1780G, |
| 1788 | 10 | c.5361_5364delTGAG, |
| 1770 | 10 | I1770V, |
| 1658 | 13 | |
| 1651 | 6 | |
| 1500 | 14 | p.K1500del, |
| 1637 | 13 | |
| 408 | 14 | |
| 253 | 13 | |
| 1792 | 14 | D1792V, D1792N, D1792Y, |
| 407 | 9 | |
| 1775 | 6 | p.F1775LfsX15, F1775V, |
| 1642 | 11 | G1642E, |
| 1655 | 11 | |
| 1790 | 14 | D1790N, p.D1790del, D1790G, |
| 406 | 12 | N406S, N406K, |
| 252 | 15 | |
| 411 | 13 | V411M, |
| 1647 | 6 | |
| 400 | 14 | G400R, G400A, G400E, |
| 1646 | 6 | |
| 1782 | 12 |