SCN5A Variant S1904L
Summary of observed carriers, functional annotations, and structural context for SCN5A S1904L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
2/61 effective observations
Estimated BrS1 penetrance
3%
1/61 effective observations
Total carriers
51
1 BrS1 · 2 LQT3 · 48 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.55 | 1 | -3.14 | 0.952 | 2 | 4 |
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 |
|---|---|---|---|---|---|---|---|
| 18708744 | 2007 | 1 | 1 | 0 | 0 | ||
| 26746457 | 2016 | 1 | 1 | 0 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 51 | 48 | 2 | 1 | – | |
| Variant features alone | – | 15 | 15 | 0 | 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 |
|---|---|---|
| 1889 | 15 | Y1889C, |
| 1890 | 14 | E1890K, |
| 1891 | 14 | |
| 1892 | 13 | |
| 1893 | 13 | c.5676delC, |
| 1894 | 12 | |
| 1895 | 11 | T1895I, |
| 1896 | 11 | p.L1896PfsX47, L1896P, |
| 1897 | 10 | R1897Y, R1897W, R1897Q, |
| 1898 | 9 | R1898H, R1898C, |
| 1899 | 8 | |
| 1900 | 8 | |
| 1901 | 7 | E1901K, E1901Q, |
| 1902 | 5 | E1902A, |
| 1903 | 4 | V1903M, |
| 1904 | 0 | S1904L, |
| 1905 | 4 | |
| 1906 | 5 | M1906V, M1906T, |
| 1907 | 7 | |
| 1908 | 8 | I1908V, |
| 1909 | 8 | Q1909R, |
| 1910 | 9 | R1910K, |
| 1911 | 10 | |
| 1912 | 11 | |
| 1913 | 11 | R1913C, R1913H, R1913S, |
| 1914 | 12 | R1914G, |
| 1915 | 13 | H1915P, H1915Y, H1915Q, H1915N, |
| 1916 | 13 | |
| 1917 | 14 | |
| 1918 | 14 | |
| 1919 | 15 | R1919H, R1919C, |