SCN5A Variant E867K

Summary of observed carriers, functional annotations, and structural context for SCN5A E867K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

31%

3/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

E867K is present in 1 alleles in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 (%)
-2.33 0.993 -0.16 0.663 43 1

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 12 0 3 – –

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 E867K.
Neighbour residue Distance (Å) Observed variants
880 13
860 13 p.L860fsx89,
911 13 G911E
864 5
870 11
862 8
867 0 E867K, E867Q, E867X,
859 13
216 14 S216X, S216L,
871 13
909 9
858 14 M858L, M858L,
877 14
869 7 R869S, R869S,
876 12
905 15
865 8
857 15 G857D,
868 6 c.2602delC, L868X,
875 11
882 11
908 13
863 5
861 12 p.F861WfsX90, c.2582_2583delTT,
906 13
881 13
866 4 S866P, S866L,
874 14 G874D,
910 10 S910L,