SCN5A Variant E1901Q

Summary of observed carriers, functional annotations, and structural context for SCN5A E1901Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1/19 effective observations

Estimated BrS1 penetrance

0/19 effective observations

Total carriers

0 BrS1 · 1 LQT3 · 8 unaffected

E1901Q is present in 8 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 (%)
-2.78	1	1.96	0.952	2	4

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	Other	Other Disease
19716085	2009	1		1	0
Literature, cohort, and gnomAD	–	9	8	1		–
Variant features alone	–	15	15	0	–	–

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)
19716085	2009
28087622	2017	HEK	83	-2.7	-4.7	392

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 E1901Q.
Neighbour residue	Distance (Å)	Observed variants
1886	15
1887	14
1888	14
1889	13	Y1889C,
1890	13	E1890K,
1891	12
1892	11
1893	11	c.5676delC,
1894	10
1895	9	T1895I,
1896	8	p.L1896PfsX47, L1896P,
1897	8	R1897Y, R1897W, R1897Q,
1898	7	R1898H, R1898C,
1899	5
1900	4
1901	0	E1901K, E1901Q,
1902	4	E1902A,
1903	5	V1903M,
1904	7	S1904L,
1905	8
1906	8	M1906V, M1906T,
1907	9
1908	10	I1908V,
1909	11	Q1909R,
1910	11	R1910K,
1911	12
1912	13
1913	13	R1913C, R1913H, R1913S,
1914	14	R1914G,
1915	14	H1915P, H1915Y, H1915Q, H1915N,
1916	15