SCN5A Variant W1345C

Summary of observed carriers, functional annotations, and structural context for SCN5A W1345C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

8%

0/13 effective observations

Estimated BrS1 penetrance

70%

9/13 effective observations

Total carriers

3

3 BrS1 · 0 LQT3 · 0 unaffected

W1345C has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 6 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 (%)
-12.67 1 -5.48 0.939 90 2

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
20339501 2010 2 0 2 0
29574140 2018 1 0 1 0
30059973 2018 2 2 0 0
Literature, cohort, and gnomAD – 3 0 0 3 –
Variant features alone – 15 9 0 6 – –

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)
30059973 2018
29574140 2018
32533946 2020 HEK 12
20339501 2010

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 W1345C.
Neighbour residue Distance (Å) Observed variants
1417 11
1352 13
1406 11 G1406R, G1406R, G1406E,
1340 8 V1340I,
1457 7
1453 7
1455 12
1757 13
1339 10 L1339F, p.L1339del,
1351 12 M1351V, M1351R,
1449 12 Y1449C, Y1449S,
1452 13
1756 13 I1756V,
1461 8 T1461S, T1461S,
812 14 L812Q,
1350 11 I1350T, I1350L,
1344 6 F1344S, F1344L, F1344L, F1344L,
731 15 T731I,
1450 12
1411 10
1451 15 V1451D, V1451L,
1353 14 V1353M
825 14
1407 12
1458 9 S1458Y,
1410 10
1348 7 F1348L, F1348L, F1348L,
1404 14
1464 12 c.4389_4396delCCTCTTTA, L1464P,
1349 8
1753 12 T1753A,
1346 7 L1346I, L1346P,
1418 13
1341 5
1334 14 I1334V,
1462 9
1412 7 L1412F,
1408 10 G1408R, G1408R,
735 14 A735V, A735T, A735E,
1456 10
1459 13 c.4376_4379delTCTT,
1460 11 F1460L, F1460L, F1460L,
816 14 F816L, F816L, F816L, F816Y,
1454 11
1338 9 L1338V,
1405 11 V1405M, V1405L, V1405L,
1409 6 Y1409X, Y1409C,
815 13
1421 15
1343 7
1345 0 W1345C, W1345C,
1337 10
1342 5
1416 8 A1416E, A1416G, c.4245+2T>A, c.4245+1G>C, c.4245+1G>A,
1465 12 p.F1465_L1480dup,
1760 14
1761 12 L1761F, c.5280delG, L1761H,
1347 8
1336 14
1415 10
1335 15 M1335R,
828 14 L828V,
1414 11 Q1414H, Q1414H,
1402 13
1463 13 N1463Y,
1413 7