SCN5A Variant R971H

Summary of observed carriers, functional annotations, and structural context for SCN5A R971H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0/16 effective observations

Estimated BrS1 penetrance

1/16 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 6 unaffected

R971H is present in 6 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_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 (%)
-0.31	0.004	0.24	0.52	12	10

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	–	6	6	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 R971H.
Neighbour residue	Distance (Å)	Observed variants
956	15	M956I, M956I, M956I, M956T,
957	14
958	14
959	13	L959P,
960	13	Q960K,
961	12
962	11
963	11
964	10	A964G,
965	9	R965C, R965L, R965H,
966	8
967	8	Q967R,
968	7
969	5	G969C, G969S,
970	4
971	0	R971C, R971H,
972	4	c.2914_2923delTTTGTCAAGC,
973	5
974	7	K974D,
975	8	R975Q, R975W,
976	8
977	9
978	10
979	11	D979H,
980	11
981	12	C981F,
982	13	C982R,
983	13	G983D,
984	14
985	14
986	15	R986L, R986Q, R986W,