SCN5A Variant E952K

Summary of observed carriers, functional annotations, and structural context for SCN5A E952K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

11%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

E952K is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-3.1 0.189 1.98 0.672 12 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 14 0 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 E952K.
Neighbour residue Distance (Å) Observed variants
937 15
938 14
939 14 L939F,
940 13 S940N,
941 13 S941F, S941N,
942 12
943 11 S943N,
944 11
945 10 D945G,
946 9
947 8
948 8
949 7
950 5 P950X,
951 4 D951X, c.2850delT,
952 0 E952K,
953 4 D953E, D953Y, D953E,
954 5 R954G,
955 7 p.E955DfsX74,
956 8 M956I, M956I, M956I, M956T,
957 8
958 9
959 10 L959P,
960 11 Q960K,
961 11
962 12
963 13
964 13 A964G,
965 14 R965C, R965H, R965L,
966 14
967 15 Q967R,