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

A1270S has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational 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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
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.

Previously observed variants near A1270S.
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