SCN5A Variant A997S

Summary of observed carriers, functional annotations, and structural context for SCN5A A997S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

22%

1/12 effective observations

Estimated BrS1 penetrance

7%

0/12 effective observations

Total carriers

2

0 BrS1 · 1 LQT3 · 1 unaffected

A997S 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 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 (%)
-0.42 0 0.24 0.488 2 13

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
11710892 2001 1 0 0 1 SIDS
19716085 2009 1 1 0 0
29544605 2018 1 0 0 1 SIDS
Literature, cohort, and gnomAD – 2 1 1 0 –
Variant features alone – 15 15 0 0 – –

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)
29544605 2018
11710892 2001 HEK 733
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 A997S.
Neighbour residue Distance (Å) Observed variants
982 15 C982R,
983 14 G983D,
984 14
985 13
986 13 R986L, R986W, R986Q,
987 12
988 11 R988Q, R988W,
989 11
990 10
991 9 K991E, K991T,
992 8
993 8 A993T, A993S,
994 7 A994V, A994T,
995 5 L995F,
996 4 A996T,
997 0 A997T, A997D, A997S,
998 4
999 5 G999D,
1000 7 Q1000X, p.Gln1000del, Q1000L,
1001 8
1002 8 c.3005-3012delCCAGCTGG, P1002S,
1003 9
1004 10 C1004R,
1005 11 I1005T, I1005V,
1006 11 A1006S,
1007 12 T1007N, T1007I,
1008 13 P1008S,
1009 13
1010 14
1011 14 P1011L, P1011S,
1012 15