SCN5A Variant E1890K

Summary of observed carriers, functional annotations, and structural context for SCN5A E1890K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0/13 effective observations

Estimated BrS1 penetrance

1/13 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 3 unaffected

E1890K is present in 3 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 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 (%)
-3.47	0.999	0.81	0.981	6	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	BrS1	Other	Other Disease
24631775	2014	1		0	1	SIDS
Literature, cohort, and gnomAD	–	3	3	0		–
Variant features alone	–	15	14	1	–	–

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V_1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID	Year	Cell Type	Peak Current (% WT)	V_1/2 Activation (mV)	V_1/2 Inactivation (mV)	Late/Persistent Current (% WT)
24631775	2014
22705208	2012

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 E1890K.
Neighbour residue	Distance (Å)	Observed variants
1875	15	M1875K, M1875T, p.M1875dup,
1876	14
1877	14	E1877K,
1878	13
1879	13
1880	12	M1880V,
1881	11
1882	11
1883	10
1884	9	P1884L,
1885	8
1886	8
1887	7
1888	5
1889	4	Y1889C,
1890	0	E1890K,
1891	4
1892	5
1893	7	c.5676delC,
1894	8
1895	8	T1895I,
1896	9	L1896P, p.L1896PfsX47,
1897	10	R1897Y, R1897Q, R1897W,
1898	11	R1898C, R1898H
1899	11
1900	12
1901	13	E1901K, E1901Q,
1902	13	E1902A,
1903	14	V1903M,
1904	14	S1904L,
1905	15