SCN5A Variant A994V

Summary of observed carriers, functional annotations, and structural context for SCN5A A994V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

6%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

A994V 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 (%)
-0.33 0.002 -0.63 0.296 1 6

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 A994V.
Neighbour residue Distance (Å) Observed variants
979 15 D979H,
980 14
981 14 C981F,
982 13 C982R,
983 13 G983D,
984 12
985 11
986 11 R986L, R986W, R986Q,
987 10
988 9 R988Q, R988W,
989 8
990 8
991 7 K991E, K991T,
992 5
993 4 A993T, A993S,
994 0 A994V, A994T,
995 4 L995F,
996 5 A996T,
997 7 A997T, A997D, A997S,
998 8
999 8 G999D,
1000 9 Q1000X, p.Gln1000del, Q1000L,
1001 10
1002 11 c.3005-3012delCCAGCTGG, P1002S,
1003 11
1004 12 C1004R,
1005 13 I1005T, I1005V,
1006 13 A1006S,
1007 14 T1007N, T1007I,
1008 14 P1008S,
1009 15