SCN5A Variant R340P

Summary of observed carriers, functional annotations, and structural context for SCN5A R340P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

32%

1/10 effective observations

Estimated BrS1 penetrance

10%

0/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

R340P has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density BrS (%)	Penetrance Density LQT3 (%)
NA	NA	NA	0.612	5	43

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	–	0	0	0	0		–
Variant features alone	–	15	14	1	0	–	–

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 R340P.
Neighbour residue	Distance (Å)	Observed variants
343	12
328	11
341	6	C341Y,
342	6
326	11
335	9	C335S, C335R, C335S,
327	10
339	7
319	12	G319S, G319R, G319C,
384	14	S384T
325	14	L325R,
317	14	K317E, K317M, K317N, K317N,
284	10
336	10	P336L,
282	9	R282C, R282H,
279	11
321	15	S321Y,
344	12	A344S,
340	0	R340W, R340Q,
338	7
285	14	T285K,
345	14
278	11	H278D, H278R,
334	12	c.999-424_1338+81del,
280	8	C280Y,
281	6	V281M,
318	15
323	14
283	5
337	11
320	12	T320N,