SCN5A Variant K991E

Summary of observed carriers, functional annotations, and structural context for SCN5A K991E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

7%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

K991E 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 (%)
-1.14 0.625 0.08 0.434 1 3

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 K991E.
Neighbour residue Distance (Å) Observed variants
976 15
977 14
978 14
979 13 D979H,
980 13
981 12 C981F,
982 11 C982R,
983 11 G983D,
984 10
985 9
986 8 R986L, R986W, R986Q,
987 8
988 7 R988Q, R988W,
989 5
990 4
991 0 K991E, K991T,
992 4
993 5 A993T, A993S,
994 7 A994V, A994T,
995 8 L995F,
996 8 A996T,
997 9 A997T, A997D, A997S,
998 10
999 11 G999D,
1000 11 Q1000X, p.Gln1000del, Q1000L,
1001 12
1002 13 c.3005-3012delCCAGCTGG, P1002S,
1003 13
1004 14 C1004R,
1005 14 I1005T, I1005V,
1006 15 A1006S,