SCN5A Variant I1968S
Summary of observed carriers, functional annotations, and structural context for SCN5A I1968S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/15 effective observations
Estimated BrS1 penetrance
14%
2/15 effective observations
Total carriers
5
1 BrS1 · 0 LQT3 · 4 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 (%) |
|---|---|---|---|---|---|
| 0.08 | 0 | 0.73 | 0.323 | 4 | 0 |
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 |
|---|---|---|---|---|---|---|---|
| 16344400 | 2005 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 5 | 4 | 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 16344400 | 2005 | HEK | 66 | 0 | -0.3 |
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 |
|---|---|---|
| 1953 | 15 | p.S1953RfsX84, |
| 1954 | 14 | E1954K, |
| 1955 | 14 | N1955Y, |
| 1956 | 13 | |
| 1957 | 13 | S1957P, |
| 1958 | 12 | R1958P, R1958X, R1958Q, |
| 1959 | 11 | |
| 1960 | 11 | |
| 1961 | 10 | |
| 1962 | 9 | P1962L, P1962S, |
| 1963 | 8 | P1963L, |
| 1964 | 8 | S1964F, |
| 1965 | 7 | S1965G, S1965N, |
| 1966 | 5 | |
| 1967 | 4 | p.S1967LfsX12, |
| 1968 | 0 | I1968N, I1968T, I1968V, I1968M, I1968S |
| 1969 | 4 | |
| 1970 | 5 | p.S1970_S1972del, |
| 1971 | 7 | |
| 1972 | 8 | |
| 1973 | 8 | F1973L, |
| 1974 | 9 | |
| 1975 | 10 | P1975T, |
| 1976 | 11 | S1976C, |
| 1977 | 11 | Y1977N, |
| 1978 | 12 | |
| 1979 | 13 | |
| 1980 | 13 | V1980F, |
| 1981 | 14 | |
| 1982 | 14 | R1982T, |
| 1983 | 15 | A1983G, A1983V, |