SCN5A Variant V1237F

Summary of observed carriers, functional annotations, and structural context for SCN5A V1237F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0/11 effective observations

Estimated BrS1 penetrance

20%

2/11 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 1 unaffected

V1237F is present in 1 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 2 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 (%)
-2.65	0.557	-0.87	0.56	26	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	13	0	2	–	–

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 V1237F.
Neighbour residue	Distance (Å)	Observed variants
1231	13	E1231K,
1241	7
1245	12	M1245I, M1245I, M1245I,
1226	15
1233	7	K1233E,
1237	0	V1237F,
1289	14
1218	15	S1218T, S1218I,
1221	12	A1221V,
1224	14
1242	9
1222	14	p.L1222LfsX7, L1222R,
1230	11	E1230K,
1243	11	D1243N,
1240	6	E1240Q,
1235	6
1234	6
1229	9
1225	11	E1225K, G1225K,
1239	7	L1239P,
1232	12	R1232W, R1232Q,
1244	11	K1244E,
1238	4
1236	5	K1236R, K1236N, K1236N,
1303	13	R1303W, R1303Q
1246	14