SCN5A Variant V1777L
Summary of observed carriers, functional annotations, and structural context for SCN5A V1777L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
48%
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 (%) |
|---|---|---|---|---|---|
| -2.7 | 0.888 | -2.59 | 0.886 | 7 | 55 |
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 |
|---|---|---|
| 414 | 11 | M414V, |
| 1785 | 10 | |
| 1778 | 4 | |
| 1480 | 14 | c.4437+5G>A, c.4438-1C>T, |
| 1773 | 7 | |
| 1653 | 11 | |
| 1771 | 11 | I1771T, |
| 1652 | 8 | M1652R, M1652T, |
| 1777 | 0 | V1777L, V1777M, |
| 1487 | 14 | M1487K, M1487L, |
| 418 | 15 | E418K, |
| 409 | 15 | L409P, L409V, |
| 1650 | 12 | L1650F, |
| 1492 | 9 | |
| 1656 | 15 | |
| 417 | 14 | |
| 1477 | 9 | K1477N, |
| 1491 | 14 | Q1491H, |
| 1471 | 14 | |
| 1779 | 6 | T1779M, |
| 1493 | 8 | K1493R, K1493X, p.K1493del, |
| 1470 | 13 | |
| 1478 | 11 | K1478E, |
| 1776 | 4 | |
| 1787 | 11 | S1787N, |
| 1786 | 12 | L1786R, L1786Q, c.5356_5357delCT, |
| 1648 | 10 | |
| 1769 | 12 | |
| 415 | 15 | A415T, |
| 1495 | 13 | Y1495S, |
| 1649 | 8 | A1649V, |
| 1774 | 6 | c.5321_5324dupACTT, N1774D, |
| 1473 | 13 | F1473C, F1473S, |
| 1496 | 9 | |
| 1474 | 10 | |
| 1481 | 12 | G1481V, G1481R, G1481E, |
| 1781 | 5 | E1781D, E1781G, |
| 1789 | 15 | |
| 1772 | 10 | L1772V, |
| 1499 | 14 | |
| 1645 | 11 | T1645M, |
| 1488 | 13 | T1488R, |
| 1784 | 12 | E1784X, E1784K, |
| 410 | 11 | A410V, |
| 1780 | 6 | E1780G, |
| 1788 | 12 | c.5361_5364delTGAG |
| 1770 | 11 | I1770V, |
| 1651 | 13 | |
| 1500 | 12 | p.K1500del, |
| 413 | 13 | A413T, A413E, |
| 1791 | 15 | |
| 1482 | 13 | |
| 407 | 14 | |
| 1783 | 10 | |
| 1476 | 15 | Q1476X, Q1476R, |
| 1775 | 7 | F1775V, p.F1775LfsX15, |
| 1642 | 14 | G1642E, |
| 1497 | 12 | |
| 1490 | 12 | |
| 1475 | 14 | p.Q1475NfsX6, Q1475L, |
| 1790 | 15 | D1790G, p.D1790del, D1790N, |
| 1494 | 15 | |
| 411 | 13 | V411M, |
| 1647 | 14 | |
| 1646 | 11 | |
| 1489 | 9 | E1489D, |
| 1782 | 9 |