SCN5A Variant A1006S

Summary of observed carriers, functional annotations, and structural context for SCN5A A1006S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

6%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

A1006S is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
0.36 0.003 0.17 0.283 2 4

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 15 0 0 – –

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 A1006S.
Neighbour residue Distance (Å) Observed variants
991 15 K991E, K991T,
992 14
993 14 A993T, A993S,
994 13 A994V, A994T,
995 13 L995F,
996 12 A996T,
997 11 A997T, A997D, A997S,
998 11
999 10 G999D,
1000 9 Q1000X, p.Gln1000del, Q1000L,
1001 8
1002 8 c.3005-3012delCCAGCTGG, P1002S,
1003 7
1004 5 C1004R,
1005 4 I1005T, I1005V,
1006 0 A1006S,
1007 4 T1007N, T1007I,
1008 5 P1008S,
1009 7
1010 8
1011 8 P1011L, P1011S,
1012 9
1013 10
1014 11 P1014S,
1015 11 p.G1015DfsX14, E1015K,
1016 12 c.3045_3046delGA, T1016M,
1017 13
1018 13 K1018E,
1019 14
1020 14
1021 15 P1021S,