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

T1461S has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 (%)
-3.82 0.83 -1.26 0.894 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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
28146213 2017
32533946 2020 HEK 60 1.1 3

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 T1461S.
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, F1344S, F1344L, F1344L,
1451 14 V1451L, V1451D,
825 13
934 10
1458 6 S1458Y,
935 11 L935P,
1762 14 p.I1762del, I1762M
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 V1468F, V1468A,
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 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
1465 7 p.F1465_L1480dup,
1760 12
1467 11
1761 10 c.5280delG, L1761F, L1761H,
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