SCN5A Variant E1954K
Summary of observed carriers, functional annotations, and structural context for SCN5A E1954K. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
9%
1/22 effective observations
Estimated BrS1 penetrance
2%
0/22 effective observations
Total carriers
12
0 BrS1 · 1 LQT3 · 11 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 (%) |
|---|---|---|---|---|---|
| -1.88 | 0.003 | 1.57 | 0.258 | 0 | 6 |
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 |
|---|---|---|---|---|---|---|---|
| 23631430 | 2013 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 12 | 11 | 1 | 0 | – | |
| 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 23631430 | 2013 |
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 |
|---|---|---|
| 1939 | 15 | p.E1939_E1943del, |
| 1940 | 14 | |
| 1941 | 14 | |
| 1942 | 13 | P1942H, P1942S |
| 1943 | 13 | |
| 1944 | 12 | R1944X, R1944Q, |
| 1945 | 11 | |
| 1946 | 11 | |
| 1947 | 10 | |
| 1948 | 9 | I1948V, |
| 1949 | 8 | A1949T, A1949S, |
| 1950 | 8 | Y1950C, |
| 1951 | 7 | V1951M, V1951L, |
| 1952 | 5 | |
| 1953 | 4 | p.S1953RfsX84, |
| 1954 | 0 | E1954K, |
| 1955 | 4 | N1955Y, |
| 1956 | 5 | |
| 1957 | 7 | S1957P, |
| 1958 | 8 | R1958Q, R1958X, R1958P, |
| 1959 | 8 | |
| 1960 | 9 | |
| 1961 | 10 | |
| 1962 | 11 | P1962L, P1962S, |
| 1963 | 11 | P1963L, |
| 1964 | 12 | S1964F, |
| 1965 | 13 | S1965G, S1965N, |
| 1966 | 13 | |
| 1967 | 14 | p.S1967LfsX12, |
| 1968 | 14 | I1968V, I1968T, I1968S, I1968N, I1968M, |
| 1969 | 15 |