SCN5A Variant T1461S
Summary of observed carriers, functional annotations, and structural context for SCN5A T1461S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
8%
0/14 effective observations
Estimated BrS1 penetrance
38%
5/14 effective observations
Total carriers
4
2 BrS1 · 0 LQT3 · 2 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
---|---|---|---|---|---|
-3.82 | 0.83 | -1.26 | 0.909 | 47 | 19 |
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 |
---|---|---|---|---|---|---|---|
28146213 | 2017 | 4 | 0 | 2 | 0 | ||
Literature, cohort, and gnomAD | – | 4 | 2 | 0 | 2 | – | |
Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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 |
---|---|---|
939 | 13 | L939F, |
896 | 14 | C896S, C896S, |
937 | 13 | |
1417 | 12 | |
1765 | 13 | |
839 | 13 | L839P, |
1340 | 7 | V1340I, |
1457 | 4 | |
1453 | 10 | |
1455 | 9 | |
1757 | 13 | |
1339 | 11 | L1339F, p.L1339del, |
1452 | 13 | |
1756 | 14 | I1756V, |
1461 | 0 | T1461S, T1461S, |
1333 | 13 | |
1344 | 7 | F1344L, F1344L, F1344S, F1344L, |
1451 | 14 | V1451L, V1451D, |
825 | 13 | |
934 | 10 | |
1458 | 6 | S1458Y, |
935 | 11 | L935P, |
1762 | 14 | I1762M, p.I1762del, |
1348 | 11 | F1348L, F1348L, F1348L, |
1464 | 5 | c.4389_4396delCCTCTTTA, L1464P, |
1466 | 11 | c.4396_4397insG, |
1349 | 15 | |
1346 | 13 | L1346I, L1346P, |
1418 | 13 | |
1341 | 5 | |
1334 | 12 | I1334V, |
1468 | 11 | V1468A, V1468F, |
831 | 13 | |
1462 | 5 | |
938 | 9 | |
1412 | 12 | L1412F, |
942 | 11 | |
1456 | 8 | |
1459 | 8 | c.4376_4379delTCTT, |
827 | 15 | |
1460 | 4 | F1460L, F1460L, F1460L, |
1454 | 10 | |
1338 | 9 | L1338V, |
1409 | 13 | Y1409C, Y1409X, |
1343 | 11 | |
1345 | 8 | W1345C, W1345C, |
941 | 13 | S941N, S941F, |
1337 | 7 | |
1342 | 10 | |
936 | 14 | |
1416 | 9 | A1416E, c.4245+2T>A, c.4245+1G>C, c.4245+1G>A, A1416G, |
1465 | 7 | p.F1465_L1480dup, |
1760 | 12 | |
1467 | 11 | |
1761 | 10 | L1761F, L1761H, c.5280delG, |
1347 | 13 | |
1469 | 13 | I1469V, |
1336 | 12 | |
1415 | 13 | |
824 | 14 | |
829 | 13 | |
932 | 15 | |
1335 | 14 | M1335R, |
832 | 11 | |
835 | 14 | S835A, S835L, |
828 | 10 | L828V, |
931 | 13 | |
1463 | 6 | N1463Y, |
1413 | 12 |