SCN5A Variant E1938K
Summary of observed carriers, functional annotations, and structural context for SCN5A E1938K. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/16 effective observations
Estimated BrS1 penetrance
14%
2/16 effective observations
Total carriers
6
1 BrS1 · 0 LQT3 · 5 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 (%) |
|---|---|---|---|---|---|
| -1.26 | 0.015 | 1.13 | 0.534 | 9 | 1 |
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 |
|---|---|---|---|---|---|---|---|
| 23853484 | 2013 | 2 | 0 | 0 | 2 | SCA, VF | |
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 6 | 5 | 0 | 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 |
|---|---|---|
| 1923 | 15 | H1923Y, H1923D, |
| 1924 | 14 | A1924T, |
| 1925 | 14 | p.S1925CfsX20, S1925F, |
| 1926 | 13 | |
| 1927 | 13 | L1927P, |
| 1928 | 12 | F1928V, |
| 1929 | 11 | R1929C, R1929H, |
| 1930 | 11 | Q1930H, |
| 1931 | 10 | |
| 1932 | 9 | A1932V, |
| 1933 | 8 | G1933D, G1933A, G1933V, |
| 1934 | 8 | |
| 1935 | 7 | G1935S |
| 1936 | 5 | |
| 1937 | 4 | S1937A, |
| 1938 | 0 | E1938X, E1938K, |
| 1939 | 4 | p.E1939_E1943del, |
| 1940 | 5 | |
| 1941 | 7 | |
| 1942 | 8 | P1942S, P1942H, |
| 1943 | 8 | |
| 1944 | 9 | R1944Q, R1944X, |
| 1945 | 10 | |
| 1946 | 11 | |
| 1947 | 11 | |
| 1948 | 12 | I1948V, |
| 1949 | 13 | A1949S, A1949T, |
| 1950 | 13 | Y1950C, |
| 1951 | 14 | V1951M, V1951L, |
| 1952 | 14 | |
| 1953 | 15 | p.S1953RfsX84, |