SCN5A Variant T427S

Summary of observed carriers, functional annotations, and structural context for SCN5A T427S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

16%

0/10 effective observations

Estimated BrS1 penetrance

11%

1/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

T427S has not been reported in gnomAD. This residue resides in a Non_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 (%)
NA	NA	NA	0.366	9	20

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	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 T427S.
Neighbour residue	Distance (Å)	Observed variants
412	15	V412D,
413	14	A413E, A413T,
414	14	M414V,
415	13	A415T,
416	13	Y416C
417	12
418	11	E418K,
419	11	Q419X,
420	10
421	9
422	8
423	8
424	7	I424M,
425	5	A425T, A425P,
426	4
427	0
428	4	E428K,
429	5	p.E429del, E429K,
430	7	K430E,
431	8
432	8
433	9	R433S, R433C, R433H,
434	10
435	11
436	11
437	12	A437V,
438	13	M438L, M438T, M438L,
439	13	E439K, E439V,
440	14
441	14	L441F,
442	15