SCN5A Variant Y1495S

Summary of observed carriers, functional annotations, and structural context for SCN5A Y1495S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

68%

4/11 effective observations

Estimated BrS1 penetrance

12%

1/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

Y1495S has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 3 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-8.28 0.662 -3.02 0.957 6 79

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
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD – 1 0 1 0 –
Variant features alone – 15 11 3 1 – –

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)
19716085 2009

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 Y1495S.
Neighbour residue Distance (Å) Observed variants
1855 14
1785 12
1778 15
1480 12 c.4438-1C>T, c.4437+5G>A,
1879 14
1486 10 p.F1486del, F1486L,
1777 13 V1777L, V1777M,
1485 12
1487 14 M1487K, M1487L,
1492 5
1504 14 K1504E,
1875 13 p.M1875dup, M1875T, M1875K,
1477 13 K1477N,
1491 7 Q1491H,
1501 10 L1501V, p.L1501_K1505del,
1874 14
1862 14
1493 9 p.K1493del, K1493R, K1493X
1858 14
1478 11 K1478E,
1787 15 S1787N,
1786 13 c.5356_5357delCT, L1786Q, L1786R,
1495 0 Y1495S,
1496 5
1481 8 G1481V, G1481E, G1481R,
1781 11 E1781G, E1781D,
1499 5
1488 12 T1488R,
1784 14 E1784X, E1784K,
1498 6 M1498V, M1498T, M1498R,
1780 15 E1780G,
1788 15 c.5361_5364delTGAG,
1500 9 p.K1500del,
1859 15
1876 11
1791 14
1482 8
1502 10 G1502A, G1502S,
1484 13
1497 7
1490 12
1483 8 Q1483H,
1494 7
1503 12 S1503Y,
1489 11 E1489D,