SCN5A Variant C1363Y

Summary of observed carriers, functional annotations, and structural context for SCN5A C1363Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/11 effective observations

Estimated BrS1 penetrance

50%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

C1363Y 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 4 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 (%)
-10.72 1 -6.05 0.957 60 0

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
16764707 2006 1 0 1 0
21273195 2011 1 0 1 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 11 0 4 – –

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)
16764707 2006
21273195 2011
20129283 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 C1363Y.
Neighbour residue Distance (Å) Observed variants
1391 9 G1391R, G1391R,
1366 10 Q1366H, Q1366R, Q1366H,
1381 7
1358 14 G1358W, G1358R, G1358R,
1396 6
1362 6 c.4083delG, R1362S, R1362S,
1433 13 G1433W, G1433R, G1433R, G1433V,
1438 8 P1438L,
1379 8
1435 13
1386 6
1394 8 Y1394X,
1360 12 F1360C,
1388 8
1430 12 D1430N,
1426 14
1393 8 L1393X,
1387 9 L1387F, L1387F,
1378 10 V1378M,
1437 6
1361 7
1384 12 C1384Y,
1431 13 S1431C,
1395 5
1382 9 S1382I,
1397 11 c.4189delT, c.4190delA,
1427 13 A1427E, A1427S,
1390 10
1363 0 C1363Y,
1365 6 N1365S,
1385 10
1380 6 p.N1380del, N1380K, N1380K
1383 11 Q1383X,
1432 13 R1432S, R1432G, R1432S,
1389 8
1439 11 Q1439H, Q1439H, Q1439R,
1392 11
1436 11
1364 4 I1364V,
1367 12
1359 14 K1359N, K1359M, K1359N,
1398 12 V1398M,