SCN5A Variant S901L
Summary of observed carriers, functional annotations, and structural context for SCN5A S901L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
0/11 effective observations
Estimated BrS1 penetrance
63%
6/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | -2.81 | None | 90 | 2 |
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 |
|---|---|---|---|---|---|---|---|
| 26173111 | 2015 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 10 | 0 | 5 | – | – |
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) |
|---|---|---|---|---|---|---|
| 26173111 | 2015 |
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 |
|---|---|---|
| 364 | 14 | |
| 891 | 13 | I891N, I891T, |
| 880 | 12 | |
| 890 | 10 | I890T, |
| 901 | 0 | E901K, S901L, |
| 919 | 11 | |
| 363 | 13 | |
| 896 | 13 | C896S, C896S, |
| 348 | 13 | P348A, |
| 895 | 15 | L895F, |
| 1426 | 14 | |
| 894 | 10 | I894M, |
| 372 | 9 | |
| 1711 | 15 | c.5131delG, |
| 904 | 7 | W904X, |
| 887 | 14 | |
| 886 | 14 | H886P, H886Q, H886Q, |
| 376 | 10 | R376C, R376H, |
| 871 | 13 | |
| 897 | 11 | G897R, G897R, G897E, |
| 909 | 13 | |
| 1423 | 12 | D1423H, |
| 876 | 14 | |
| 1422 | 9 | M1422R, |
| 1418 | 14 | |
| 902 | 5 | |
| 892 | 14 | F892I, |
| 349 | 9 | D349N, |
| 373 | 8 | |
| 1712 | 15 | G1712S, G1712C |
| 881 | 13 | |
| 898 | 7 | |
| 893 | 7 | R893C, R893H, |
| 922 | 15 | V922I, |
| 920 | 15 | |
| 889 | 13 | |
| 1420 | 12 | G1420R, G1420D, G1420V, G1420P, |
| 900 | 6 | |
| 872 | 13 | D872N, |
| 918 | 15 | |
| 1425 | 14 | |
| 865 | 13 | |
| 916 | 14 | |
| 906 | 10 | |
| 351 | 13 | G351S, G351C, G351D, G351V, |
| 910 | 15 | S910L, |
| 878 | 9 | R878C, R878H, R878L, |
| 1421 | 11 | |
| 374 | 15 | W374G, |
| 350 | 8 | H350Q, H350Q, |
| 903 | 8 | p.M903CfsX29, |
| 367 | 11 | R367C, R367H, R367L, |
| 370 | 14 | T370M, |
| 877 | 10 | |
| 879 | 8 | W879R, W879R, |
| 923 | 14 | |
| 905 | 6 | |
| 375 | 12 | |
| 352 | 12 | Y352C, |
| 915 | 12 | C915R, |
| 899 | 9 | |
| 380 | 15 | |
| 377 | 13 | |
| 908 | 11 | |
| 861 | 15 | p.F861WfsX90, c.2582_2583delTT, |
| 1419 | 12 | K1419E, |
| 353 | 12 | T353I, |
| 907 | 11 |