SCN5A Variant R504K

Summary of observed carriers, functional annotations, and structural context for SCN5A R504K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

16%

0/10 effective observations

Estimated BrS1 penetrance

0/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

R504K 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 0 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	0.369	5	21

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	15	0	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 R504K.
Neighbour residue	Distance (Å)	Observed variants
489	15
490	14	G490E, G490A,
491	14	E491G,
492	13
493	13	R493K,
494	12
495	11
496	11	K496M, K496N, K496N,
497	10	S497C,
498	9
499	8
500	8	E500K,
501	7	D501G,
502	5
503	4	P503S,
504	0	R504T,
505	4	A505E,
506	5	M506K,
507	7	p.N507_L515dup,
508	8
509	8
510	9
511	10
512	11	T512I,
513	11	R513C, c.1537delC, R513H, R513P,
514	12	G514C,
515	13
516	13
517	14	R517S, R517S,
518	14
519	15	S519F