SCN5A Variant G1935S
Summary of observed carriers, functional annotations, and structural context for SCN5A G1935S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
16%
2/20 effective observations
Estimated BrS1 penetrance
11%
2/20 effective observations
Total carriers
10
1 BrS1 · 2 LQT3 · 7 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -0.78 | 0.001 | 1.23 | 0.592 | 6 | 11 |
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 |
|---|---|---|---|---|---|---|---|
| 18508782 | 2008 | 1 | 0 | 0 | 1 | SD | |
| 20541041 | 2010 | 1 | 1 | 0 | 0 | ||
| 27816319 | 2017 | 1 | 1 | 0 | 0 | ||
| 26746457 | 2016 | 1 | 1 | 0 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 10 | 7 | 2 | 1 | – | |
| Variant features alone | – | 15 | 14 | 0 | 1 | – | – |
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 |
|---|---|---|
| 1920 | 15 | S1920C, |
| 1921 | 14 | |
| 1922 | 14 | K1922N, K1922R, |
| 1923 | 13 | H1923D, H1923Y, |
| 1924 | 13 | A1924T, |
| 1925 | 12 | p.S1925CfsX20, S1925F, |
| 1926 | 11 | |
| 1927 | 11 | L1927P, |
| 1928 | 10 | F1928V, |
| 1929 | 9 | R1929C, R1929H, |
| 1930 | 8 | Q1930H, |
| 1931 | 8 | |
| 1932 | 7 | A1932V, |
| 1933 | 5 | G1933A, G1933D, G1933V, |
| 1934 | 4 | |
| 1935 | 0 | G1935S, |
| 1936 | 4 | |
| 1937 | 5 | S1937A, |
| 1938 | 7 | E1938X, E1938K, |
| 1939 | 8 | p.E1939_E1943del, |
| 1940 | 8 | |
| 1941 | 9 | |
| 1942 | 10 | P1942H, P1942S |
| 1943 | 11 | |
| 1944 | 11 | R1944X, R1944Q, |
| 1945 | 12 | |
| 1946 | 13 | |
| 1947 | 13 | |
| 1948 | 14 | I1948V, |
| 1949 | 14 | A1949T, A1949S, |
| 1950 | 15 | Y1950C, |