SCN5A Variant W1095C
Summary of observed carriers, functional annotations, and structural context for SCN5A W1095C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
17%
1/14 effective observations
Estimated BrS1 penetrance
8%
1/14 effective observations
Total carriers
4
0 BrS1 · 1 LQT3 · 3 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 (%) |
---|---|---|---|---|---|
-0.88 | 0.651 | 0.83 | 0.606 | 6 | 12 |
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 |
---|---|---|---|---|---|---|---|
26669661 | 2016 | 2 | 1 | 0 | 0 | ||
29574140 | 2018 | 1 | 0 | 1 | 0 | ||
Literature, cohort, and gnomAD | – | 4 | 3 | 1 | 0 | – | |
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 |
---|---|---|
1080 | 15 | |
1081 | 14 | |
1082 | 14 | V1082A, |
1083 | 13 | S1083C, |
1084 | 13 | G1084R, G1084D, G1084S |
1085 | 12 | |
1086 | 11 | |
1087 | 11 | |
1088 | 10 | A1088V, A1088T, |
1089 | 9 | |
1090 | 8 | P1090L, P1090Q, |
1091 | 8 | D1091A, D1091Y, |
1092 | 7 | |
1093 | 5 | |
1094 | 4 | |
1095 | 0 | W1095C, W1095C, W1095X, |
1096 | 4 | S1096C, S1096G, |
1097 | 5 | c.3288+2delT, Q1097H, Q1097H, |
1098 | 7 | V1098M, V1098L, V1098L, |
1099 | 8 | |
1100 | 8 | A1100T, A1100V, |
1101 | 9 | |
1102 | 10 | A1102T, |
1103 | 11 | S1103Y, S1103F, |
1104 | 11 | |
1105 | 12 | E1105V, E1105X, |
1106 | 13 | A1106T, |
1107 | 13 | p.E1107RfsX24, E1107K, E1107X, |
1108 | 14 | |
1109 | 14 | S1109G, |
1110 | 15 |