SCN5A Variant R1898H

Summary of observed carriers, functional annotations, and structural context for SCN5A R1898H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0/22 effective observations

Estimated BrS1 penetrance

1/22 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 12 unaffected

R1898H is present in 12 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 (%)
-3.24	0.96	-1.49	0.802	13	2

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
28069705	2017	1		0	1	ARVD
25163546	2015	1		0	1	DCM
Literature, cohort, and gnomAD	–	12	12	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)
25163546	2015
28069705	2017	hiPSC	68	0	0

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 R1898H.
Neighbour residue	Distance (Å)	Observed variants
1883	15
1884	14	P1884L,
1885	14
1886	13
1887	13
1888	12
1889	11	Y1889C,
1890	11	E1890K,
1891	10
1892	9
1893	8	c.5676delC,
1894	8
1895	7	T1895I,
1896	5	L1896P, p.L1896PfsX47,
1897	4	R1897Y, R1897Q, R1897W,
1898	0	R1898C, R1898H
1899	4
1900	5
1901	7	E1901K, E1901Q,
1902	8	E1902A,
1903	8	V1903M,
1904	9	S1904L,
1905	10
1906	11	M1906T, M1906V,
1907	11
1908	12	I1908V,
1909	13	Q1909R,
1910	13	R1910K,
1911	14
1912	14
1913	15	R1913S, R1913H, R1913C,