SCN5A Variant E763D

Summary of observed carriers, functional annotations, and structural context for SCN5A E763D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

15%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

E763D 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 (%)
-2.97 0.003 0.24 0.729 22 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 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 E763D.
Neighbour residue Distance (Å) Observed variants
719 7
723 7 I723V,
710 9
766 6
758 8 G758E,
769 11
760 7 p.F760SfsX5,
776 11 p.Y776del,
721 12
765 7
759 6 p.I759FfsX6, I759V, c.2274delG,
792 14
764 5 M764K, M764R,
755 12
777 15 F777L, F777L, F777L,
726 10
781 15 W781X,
720 9
788 12 I788V,
711 13
724 12 T724I,
782 11 N782T
793 15 L793F,
820 14
713 9
712 14
762 4
727 12
767 6
717 14 P717L,
770 11
756 11
814 13 R814Q,
722 9
757 11
768 10
786 12
817 12 K817E,
761 7
716 11
790 15
715 14 M715I, M715I, M715I, M715T,
725 13
784 14 F784L, F784L, F784L,
763 0 E763K, E763D, E763D,
771 12 L771V,
785 10 D785N,
730 14 N730K, N730K,
789 10 V789A, V789I,
714 9 V714D, V714A,
718 13 F718L, F718L, F718L,