SCN5A Variant S941F
Summary of observed carriers, functional annotations, and structural context for SCN5A S941F. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
55%
3/11 effective observations
Estimated BrS1 penetrance
8%
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 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.86 | 0.999 | -3.27 | 0.931 | 1 | 62 |
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 | 2 | 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.
| 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 |
|---|---|---|
| 939 | 7 | L939F, |
| 937 | 6 | |
| 839 | 10 | L839P, |
| 842 | 12 | |
| 943 | 6 | S943N, |
| 1461 | 13 | T1461S, T1461S, |
| 836 | 11 | V836M, |
| 417 | 11 | |
| 934 | 10 | |
| 933 | 12 | |
| 1471 | 11 | |
| 935 | 11 | L935P, |
| 1470 | 13 | |
| 1464 | 10 | c.4389_4396delCCTCTTTA, L1464P, |
| 1466 | 13 | c.4396_4397insG, |
| 944 | 9 | |
| 830 | 11 | |
| 833 | 10 | G833R, G833R, |
| 940 | 4 | S940N, |
| 1468 | 12 | V1468F, V1468A, |
| 831 | 6 | |
| 420 | 10 | |
| 938 | 6 | |
| 840 | 13 | |
| 942 | 4 | |
| 843 | 15 | T843A, |
| 419 | 15 | Q419X, |
| 834 | 8 | N834D, |
| 827 | 11 | |
| 1460 | 10 | F1460L, F1460L, F1460L, |
| 837 | 11 | |
| 239 | 14 | I239V, I239V , |
| 416 | 10 | Y416C, |
| 413 | 13 | A413T, A413E, |
| 841 | 14 | p.N841TfsX2, N841K, N841K, |
| 941 | 0 | S941N, S941F, |
| 1337 | 15 | |
| 936 | 8 | |
| 238 | 13 | |
| 838 | 9 | |
| 1467 | 10 | |
| 1465 | 15 | p.F1465_L1480dup, |
| 421 | 13 | |
| 1469 | 15 | I1469V |
| 829 | 12 | |
| 932 | 15 | |
| 832 | 9 | |
| 835 | 7 | S835A, S835L, |
| 828 | 10 | L828V, |
| 1463 | 13 | N1463Y, |