SCN5A Variant V1951L
Summary of observed carriers, functional annotations, and structural context for SCN5A V1951L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
0%
4/1753 effective observations
Estimated BrS1 penetrance
0%
2/1753 effective observations
Total carriers
1743
2 BrS1 · 4 LQT3 · 1737 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 (%) |
|---|---|---|---|---|---|
| 0.24 | 0 | -0.14 | 0.337 | 1 | 5 |
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 |
|---|---|---|---|---|---|---|---|
| 17210841 | 2007 | 1 | 0 | 0 | 1 | SIDS | |
| 11901046 | 2002 | 1 | 0 | 1 | 0 | ||
| 14967853 | 2004 | 1 | 0 | 1 | 0 | ||
| 16379539 | 2005 | 2 | 2 | 0 | 0 | ||
| 20625312 | 2010 | 1 | 0 | 1 | 0 | ||
| 20636320 | 2011 | 1 | 1 | 0 | 0 | ||
| 22677073 | 2012 | 2 | 0 | 0 | 2 | SUDS | |
| 24687331 | 2014 | 1 | 1 | 0 | 0 | ||
| 23571586 | 2013 | 1 | 0 | 0 | 1 | stillbirth, SUDS | |
| 20129283 | 2010 | 16 | 0 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1743 | 1737 | 4 | 2 | – | |
| 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) |
|---|---|---|---|---|---|---|
| 10807545 | 2000 | |||||
| 11901046 | 2002 | |||||
| 14967853 | 2004 | |||||
| 15851227 | 2004 | |||||
| 15898185 | 2004 | |||||
| 16379539 | 2005 | |||||
| 20625312 | 2010 | |||||
| 20636320 | 2011 | |||||
| 22677073 | 2012 | |||||
| 24687331 | 2014 | |||||
| 21109022 | 2011 | |||||
| 22378279 | 2012 | |||||
| 23465283 | 2013 | |||||
| 23571586 | 2013 | |||||
| 15992733 | 2005 | |||||
| 17646591 | 2007 | |||||
| 20129283 | 2010 | |||||
| 15992732 | 2005 | HEK | 124 | -1 | 3 | |
| 17210841 | 2007 | tsA207 | 150 | -1.6 | 1.8 | 168 |
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 |
|---|---|---|
| 1936 | 15 | |
| 1937 | 14 | S1937A, |
| 1938 | 14 | E1938X, E1938K, |
| 1939 | 13 | p.E1939_E1943del, |
| 1940 | 13 | |
| 1941 | 12 | |
| 1942 | 11 | P1942H, P1942S |
| 1943 | 11 | |
| 1944 | 10 | R1944X, R1944Q, |
| 1945 | 9 | |
| 1946 | 8 | |
| 1947 | 8 | |
| 1948 | 7 | I1948V, |
| 1949 | 5 | A1949T, A1949S, |
| 1950 | 4 | Y1950C, |
| 1951 | 0 | V1951M, V1951L, |
| 1952 | 4 | |
| 1953 | 5 | p.S1953RfsX84, |
| 1954 | 7 | E1954K, |
| 1955 | 8 | N1955Y, |
| 1956 | 8 | |
| 1957 | 9 | S1957P, |
| 1958 | 10 | R1958Q, R1958X, R1958P, |
| 1959 | 11 | |
| 1960 | 11 | |
| 1961 | 12 | |
| 1962 | 13 | P1962L, P1962S, |
| 1963 | 13 | P1963L, |
| 1964 | 14 | S1964F, |
| 1965 | 14 | S1965G, S1965N, |
| 1966 | 15 |