SCN5A Variant M1652R
Summary of observed carriers, functional annotations, and structural context for SCN5A M1652R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
74%
4/11 effective observations
Estimated BrS1 penetrance
9%
0/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 3 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.58 | 0.999 | -1.19 | 0.958 | 5 | 93 |
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 |
|---|---|---|---|---|---|---|---|
| 17698727 | 2007 | 1 | 1 | 0 | 0 | ||
| 26940925 | 2016 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 12 | 3 | 0 | – | – |
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 | 12 | |
| 1659 | 14 | |
| 1643 | 14 | I1643L, |
| 1778 | 8 | |
| 1480 | 14 | c.4437+5G>A, c.4438-1C>T, |
| 1773 | 10 | |
| 1653 | 5 | |
| 1771 | 9 | I1771T, |
| 1652 | 0 | M1652R, M1652T, |
| 1634 | 14 | L1634P, |
| 1777 | 8 | V1777L, V1777M, |
| 1650 | 7 | L1650F, |
| 1492 | 14 | |
| 1656 | 9 | |
| 1477 | 11 | K1477N, |
| 1779 | 12 | T1779M, |
| 1493 | 15 | K1493R, K1493X, p.K1493del, |
| 1776 | 10 | |
| 1787 | 11 | S1787N, |
| 1767 | 13 | Y1767C, |
| 1660 | 15 | I1660S, I1660V, |
| 1654 | 8 | |
| 1786 | 15 | L1786R, L1786Q, c.5356_5357delCT, |
| 1648 | 5 | |
| 1769 | 13 | |
| 1319 | 13 | G1319V, |
| 1649 | 4 | A1649V, |
| 1768 | 15 | I1768V, |
| 1774 | 5 | c.5321_5324dupACTT, N1774D, |
| 1473 | 14 | F1473C, F1473S, |
| 1644 | 12 | R1644C, R1644H, R1644L, |
| 1657 | 10 | |
| 1496 | 12 | |
| 1474 | 15 | |
| 1481 | 14 | G1481V, G1481R, G1481E, |
| 1781 | 10 | E1781D, E1781G, |
| 1789 | 13 | |
| 1318 | 14 | |
| 1772 | 12 | L1772V, |
| 1499 | 15 | |
| 1645 | 10 | T1645M, |
| 410 | 14 | A410V, |
| 1780 | 14 | E1780G, |
| 1788 | 9 | c.5361_5364delTGAG |
| 1770 | 9 | I1770V, |
| 1651 | 6 | |
| 1500 | 12 | p.K1500del, |
| 1791 | 14 | |
| 1322 | 14 | c.3963+4A>G, c.3963+2T>C, |
| 1792 | 14 | D1792N, D1792V, D1792Y, |
| 407 | 13 | |
| 1775 | 9 | F1775V, p.F1775LfsX15, |
| 1642 | 15 | G1642E, |
| 1655 | 8 | |
| 1497 | 15 | |
| 1790 | 15 | D1790G, p.D1790del, D1790N, |
| 406 | 14 | N406S, N406K, |
| 1647 | 10 | |
| 1503 | 15 | S1503Y, |
| 1646 | 10 | |
| 1782 | 14 | |
| 1658 | 12 |