SCN5A Variant A1270S
Summary of observed carriers, functional annotations, and structural context for SCN5A A1270S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
9%
0/11 effective observations
Estimated BrS1 penetrance
14%
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 (%) |
|---|---|---|---|---|---|
| -2.75 | 0.877 | 1.06 | 0.743 | 19 | 10 |
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 |
|---|---|---|
| 1267 | 10 | |
| 1328 | 11 | V1328M, |
| 1271 | 5 | W1271C, |
| 1315 | 12 | |
| 1274 | 6 | |
| 1258 | 14 | |
| 1272 | 5 | |
| 1270 | 0 | A1270S, |
| 1309 | 12 | R1309H, R1309C, |
| 1265 | 11 | |
| 1313 | 14 | |
| 1279 | 14 | V1279I, |
| 1329 | 14 | G1329S, |
| 1310 | 14 | |
| 1316 | 14 | R1316Q, R1316L, |
| 1305 | 14 | |
| 1273 | 6 | c.3816delG, W1273C, |
| 1262 | 13 | G1262S, |
| 1324 | 13 | |
| 1327 | 14 | |
| 1257 | 13 | |
| 1268 | 7 | T1268S, T1268N, |
| 1275 | 9 | D1275N, |
| 1254 | 14 | |
| 1263 | 13 | |
| 1264 | 14 | K1264R, K1264N, |
| 1312 | 9 | |
| 1280 | 14 | |
| 1311 | 11 | L1311P, |
| 1308 | 11 | L1308F, |
| 1331 | 14 | I1331V, |
| 1269 | 4 | N1269S, |
| 1325 | 13 | N1325S, |
| 1276 | 10 | |
| 1278 | 12 | I1278N, |
| 1266 | 9 | |
| 1261 | 12 | |
| 1277 | 10 |