SCN5A Variant c.4437+5G>A
Summary of observed carriers, functional annotations, and structural context for SCN5A c.4437+5G>A. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
13%
1/15 effective observations
Estimated BrS1 penetrance
38%
5/15 effective observations
Total carriers
5
3 BrS1 · 0 LQT3 · 2 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 34 | 32 |
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 |
|---|---|---|---|---|---|---|---|
| 19251209 | 2009 | 1 | 0 | 1 | 0 | ||
| 21273195 | 2011 | 2 | 0 | 2 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| 29709101 | 2018 | 2 | 0 | 0 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 5 | 2 | 0 | 3 | – | |
| Variant features alone | – | 15 | 12 | 1 | 2 | – | – |
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 |
|---|---|---|
| 1659 | 14 | |
| 1480 | 0 | c.4437+5G>A, c.4438-1C>T, |
| 1773 | 12 | |
| 1653 | 14 | |
| 1472 | 13 | p.N1472del, N1472S, |
| 1315 | 15 | |
| 1652 | 14 | M1652T, M1652R, |
| 1777 | 14 | V1777M, V1777L, V1777L |
| 1485 | 15 | |
| 1320 | 13 | M1320I, M1320I, M1320I, |
| 1492 | 12 | |
| 1656 | 12 | |
| 1477 | 6 | K1477N, K1477N, |
| 1478 | 8 | K1478E, |
| 1329 | 15 | G1329S, |
| 1769 | 15 | |
| 1319 | 10 | G1319V, |
| 1495 | 12 | Y1495S, |
| 1774 | 13 | N1774D, c.5321_5324dupACTT, |
| 1479 | 6 | |
| 1473 | 11 | F1473S, F1473C, |
| 1496 | 12 | |
| 1474 | 11 | |
| 1324 | 13 | |
| 1481 | 4 | G1481R, G1481R, G1481E, G1481V, |
| 1317 | 14 | F1317C, |
| 1318 | 10 | |
| 1499 | 13 | |
| 1321 | 9 | R1321K, |
| 1323 | 11 | V1323G, |
| 1770 | 13 | I1770V, |
| 1482 | 7 | |
| 1322 | 7 | c.3963+2T>C, c.3963+4A>G, |
| 1326 | 12 | A1326S, |
| 1476 | 6 | Q1476X, Q1476R, |
| 1484 | 12 | |
| 1655 | 14 | |
| 1475 | 9 | p.Q1475NfsX6, Q1475L, |
| 1483 | 11 | Q1483H, Q1483H, |
| 1325 | 10 | N1325S, |