SCN5A Variant A1949S
Summary of observed carriers, functional annotations, and structural context for SCN5A A1949S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
38%
2/11 effective observations
Estimated BrS1 penetrance
8%
0/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -1.36 | 0.95 | 1.59 | 0.831 | 0 | 34 |
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 |
|---|---|---|---|---|---|---|---|
| 15840476 | 2005 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 14 | 1 | 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) |
|---|---|---|---|---|---|---|
| 15840476 | 2005 |
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 |
|---|---|---|
| 1934 | 15 | |
| 1935 | 14 | G1935S, |
| 1936 | 14 | |
| 1937 | 13 | S1937A, |
| 1938 | 13 | E1938X, E1938K, |
| 1939 | 12 | p.E1939_E1943del, |
| 1940 | 11 | |
| 1941 | 11 | |
| 1942 | 10 | P1942H, P1942S |
| 1943 | 9 | |
| 1944 | 8 | R1944X, R1944Q, |
| 1945 | 8 | |
| 1946 | 7 | |
| 1947 | 5 | |
| 1948 | 4 | I1948V, |
| 1949 | 0 | A1949T, A1949S, |
| 1950 | 4 | Y1950C, |
| 1951 | 5 | V1951M, V1951L, |
| 1952 | 7 | |
| 1953 | 8 | p.S1953RfsX84, |
| 1954 | 8 | E1954K, |
| 1955 | 9 | N1955Y, |
| 1956 | 10 | |
| 1957 | 11 | S1957P, |
| 1958 | 11 | R1958Q, R1958X, R1958P, |
| 1959 | 12 | |
| 1960 | 13 | |
| 1961 | 13 | |
| 1962 | 14 | P1962L, P1962S, |
| 1963 | 14 | P1963L, |
| 1964 | 15 | S1964F, |