SCN5A Variant E1015K

Summary of observed carriers, functional annotations, and structural context for SCN5A E1015K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

19%

1/11 effective observations

Estimated BrS1 penetrance

16%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

E1015K is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-0.79 0.005 -0.72 0.495 17 33

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 13 1 1 – –

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 E1015K.
Neighbour residue Distance (Å) Observed variants
1000 15 Q1000X, p.Gln1000del, Q1000L,
1001 14
1002 14 c.3005-3012delCCAGCTGG, P1002S,
1003 13
1004 13 C1004R,
1005 12 I1005V, I1005T,
1006 11 A1006S,
1007 11 T1007I, T1007N,
1008 10 P1008S,
1009 9
1010 8
1011 8 P1011S, P1011L,
1012 7
1013 5
1014 4 P1014S,
1015 0 E1015K, p.G1015DfsX14,
1016 4 T1016M, c.3045_3046delGA,
1017 5
1018 7 K1018E,
1019 8
1020 8
1021 9 P1021S,
1022 10
1023 11 R1023P, R1023H, R1023C,
1024 11 K1024R,
1025 12 E1025A,
1026 13
1027 13 R1027P, R1027W, R1027Q,
1028 14
1029 14 E1029K,
1030 15