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 |