SCN5A Variant S1503Y

Summary of observed carriers, functional annotations, and structural context for SCN5A S1503Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

24%

1/11 effective observations

Estimated BrS1 penetrance

12%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

S1503Y is present in 1 alleles 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 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-5.41 0.783 0.37 0.921 10 34

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
Literature, cohort, and gnomAD 1 1 0 0
Variant features alone 15 13 1 1

Totals may differ from individual publications due to duplicate patients removed during curation.

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 S1503Y.
Neighbour residue Distance (Å) Observed variants
1850 11 C1850S, C1850S,
1855 13
1794 12
1849 13 H1849R,
1853 14 I1853V
1795 10 Y1795N, Y1795H, p.Y1795_E1796insD, Y1795C,
1652 15 M1652T, M1652R,
1504 4 K1504E,
1851 9 M1851V, M1851I, M1851I, M1851I,
1501 7 p.L1501_K1505del, L1501V,
1507 13 p.Q1507_P1509del,
1505 7 p.K1505_Q1507del, K1505N, K1505N,
1858 13
1787 13 S1787N,
1786 13 c.5356_5357delCT, L1786Q, L1786R,
1648 15
1807 13 c.5420dupA,
1495 12 Y1495S,
1798 14 W1798X,
1496 11
1854 10
1481 15 G1481R, G1481R, G1481E, G1481V,
1781 15 E1781G, E1781D, E1781D,
1789 14
1499 6
1498 10 M1498V, M1498T, M1498R,
1788 10 c.5361_5364delTGAG,
1500 6 p.K1500del,
1791 9
1852 14 D1852V,
1792 11 D1792N, D1792Y, D1792V,
1502 4 G1502S, G1502A,
1497 9
1790 14 D1790N, D1790G, p.D1790del,
1494 14
1506 10 P1506T, P1506S,
1503 0 S1503Y,