SCN5A Variant Q421K

Summary of observed carriers, functional annotations, and structural context for SCN5A Q421K. 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

Q421K 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	0.603	8	19

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 Q421K.
Neighbour residue	Distance (Å)	Observed variants
414	11	M414V,
939	13	L939F,
937	14
943	14	S943N,
418	7	E418K,
237	14
417	5
1779	14	T1779M,
412	14	V412D,
245	14	Q245K,
1776	14
415	10	A415T,
940	10	S940N,
420	5
241	14
419	7	Q419X,
423	7
1488	14	T1488R,
239	14	I239V, I239V ,
1780	12	E1780G,
242	13	A242D,
416	9	Y416C,
413	12	A413E, A413T,
941	13	S941F, S941N,
1783	13
936	13
238	11
422	5
421	0
1490	13
1489	13	E1489D, E1489D,