SCN5A Variant E1877K

Summary of observed carriers, functional annotations, and structural context for SCN5A E1877K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0/11 effective observations

Estimated BrS1 penetrance

0/11 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 1 unaffected

E1877K 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 (%)
-3.55	0.668	1.7	0.849	4	0

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 E1877K.
Neighbour residue	Distance (Å)	Observed variants
1855	10
1875	7	M1875T, p.M1875dup, M1875K,
1872	9	K1872N, K1872N,
1884	12	P1884L,
1878	6
1491	13	Q1491H, Q1491H
1871	11
1856	12
1860	15	c.5577_5578dupAA,
1874	5
1862	13
1837	15
1863	13
1867	13
1858	14
1873	5	I1873V,
1879	8
1881	8
1877	0	E1877K,
1882	10
1885	14
1870	12	A1870T,
1883	12
1498	12	M1498T, M1498V, M1498R,
1839	11	D1839G,
1880	6	M1880V,
1866	15
1494	11
1838	13
1859	8
1869	11
1876	6
1868	14