SCN5A Variant S835A

Summary of observed carriers, functional annotations, and structural context for SCN5A S835A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

9%

0/13 effective observations

Estimated BrS1 penetrance

21%

2/13 effective observations

Total carriers

3

0 BrS1 · 0 LQT3 · 3 unaffected

S835A is present in 3 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 2 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 (%)
-2.97 0.895 0.47 0.906 38 17

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 3 3 0 0
Variant features alone 15 13 0 2

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 S835A.
Neighbour residue Distance (Å) Observed variants
939 13 L939F,
937 8
839 5 L839P,
842 10
943 13 S943N,
1455 14
1461 14 T1461S, T1461S,
836 4 V836M,
826 15 N826D,
234 12 P234S,
934 10
933 13
935 14 L935P,
1464 13 c.4389_4396delCCTCTTTA, L1464P
944 14
845 15 c.2533delG,
830 10
833 5 G833R, G833R,
940 10 S940N,
831 7
420 13
938 9
235 12 c.703+1G>A, G235R, G235R, c.704-1G>C,
840 8
942 9
843 11 T843A,
1456 12
1459 15 c.4376_4379delTCTT,
834 5 N834D,
827 13
1460 10 F1460L, F1460L, F1460L,
837 5
239 13 I239V, I239V ,
416 13 Y416C,
841 9 p.N841TfsX2, N841K, N841K,
941 7 S941N, S941F,
936 12
238 12
233 14
838 5
844 13 L844RfsX3,
829 10
832 5
835 0 S835A, S835L,
828 10 L828V,
1463 15 N1463Y,