SCN5A Variant R1195S
Summary of observed carriers, functional annotations, and structural context for SCN5A R1195S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
11%
0/11 effective observations
Estimated BrS1 penetrance
11%
1/11 effective observations
Total carriers
1
0 BrS1 · 0 LQT3 · 1 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 (%) |
|---|---|---|---|---|---|
| -5.85 | 0.997 | -4.7 | 0.86 | 6 | 16 |
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 |
|---|---|---|---|---|---|---|---|
| 26746457 | 2016 | 1 | 0 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 1 | 0 | 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 26746457 | 2016 |
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 |
|---|---|---|
| 1180 | 15 | A1180V, |
| 1181 | 14 | V1181M, V1181A, V1181L, V1181L |
| 1182 | 14 | |
| 1183 | 13 | T1183I, |
| 1184 | 13 | |
| 1185 | 12 | c.3553_3554delCA, |
| 1186 | 11 | A1186T, |
| 1187 | 11 | P1187Q, |
| 1188 | 10 | |
| 1189 | 9 | K1189T, |
| 1190 | 8 | V1190F, |
| 1191 | 8 | W1191X, |
| 1192 | 7 | W1192X, |
| 1193 | 5 | R1193Q, R1193W, |
| 1194 | 4 | L1194M, |
| 1195 | 0 | R1195S, R1195H, |
| 1196 | 4 | |
| 1197 | 5 | |
| 1198 | 7 | |
| 1199 | 8 | Y1199S, |
| 1200 | 8 | p.H1200PfsX41, H1200R, H1200Y, |
| 1201 | 9 | I1201M, |
| 1202 | 10 | V1202M, |
| 1203 | 11 | |
| 1204 | 11 | |
| 1205 | 12 | |
| 1206 | 13 | |
| 1207 | 13 | |
| 1208 | 14 | E1208X, E1208K, |
| 1209 | 14 | T1209R, |
| 1210 | 15 | F1210S, |