SCN5A Variant P1008S

Summary of observed carriers, functional annotations, and structural context for SCN5A P1008S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

38%

3/13 effective observations

Estimated BrS1 penetrance

13%

1/13 effective observations

Total carriers

3

0 BrS1 · 2 LQT3 · 1 unaffected

P1008S is present in 1 alleles in gnomAD. This residue resides in a Non_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 (%)
-0.17 0 -0.3 0.513 2 32

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
20025708 2010 4 0 0 4 CCD
24667783 2015 1 1 0 0
27566755 2016 1 1 0 0
Literature, cohort, and gnomAD – 3 1 2 0 –
Variant features alone – 15 13 1 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)
20025708 2010 tsA201 12 1.37
27566755 2016
24667783 2015

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 P1008S.
Neighbour residue Distance (Å) Observed variants
993 15 A993T, A993S,
994 14 A994V, A994T,
995 14 L995F,
996 13 A996T,
997 13 A997T, A997D, A997S,
998 12
999 11 G999D,
1000 11 Q1000X, p.Gln1000del, Q1000L,
1001 10
1002 9 c.3005-3012delCCAGCTGG, P1002S,
1003 8
1004 8 C1004R,
1005 7 I1005T, I1005V,
1006 5 A1006S,
1007 4 T1007N, T1007I,
1008 0 P1008S,
1009 4
1010 5
1011 7 P1011L, P1011S,
1012 8
1013 8
1014 9 P1014S,
1015 10 p.G1015DfsX14, E1015K,
1016 11 c.3045_3046delGA, T1016M,
1017 11
1018 12 K1018E,
1019 13
1020 13
1021 14 P1021S,
1022 14
1023 15 R1023H, R1023P, R1023C,