SCN5A Variant C489F

Summary of observed carriers, functional annotations, and structural context for SCN5A C489F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0/10 effective observations

Estimated BrS1 penetrance

0/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

C489F has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_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	0.215	1	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	–	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 C489F.
Neighbour residue	Distance (Å)	Observed variants
474	15	R474K, R474G,
475	14	R475K, R475S,
476	14
477	13	c.1428_1431delCAAG
478	13
479	12
480	11	K480N,
481	11	R481W, R481Q,
482	10	M482I,
483	9
484	8
485	8
486	7	T486S, T486A,
487	5
488	4
489	0
490	4	G490A, G490E,
491	5	E491G,
492	7
493	8	R493K,
494	8
495	9
496	10	K496M, K496N,
497	11	S497C,
498	11
499	12
500	13	E500K,
501	13	D501G,
502	14
503	14	P503S,
504	15	R504T,