SCN5A Variant G599R

Summary of observed carriers, functional annotations, and structural context for SCN5A G599R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/12 effective observations

Estimated BrS1 penetrance

9%

1/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

G599R is present in 2 alleles 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 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 (%)
-6.36 1 1.74 0.855 0 1

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 – 2 2 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 G599R.
Neighbour residue Distance (Å) Observed variants
584 15 G584R,
585 14
586 14 p.586_587delAL, A586T, A586G,
587 13
588 13 H588N, H588R,
589 12
590 11 K590Q,
591 11
592 10 N592S, N592K, N592K,
593 9
594 8
595 8
596 7 D596G,
597 5 C597G, C597Y,
598 4
599 0 G599R, G599R,
600 4
601 5 V601A,
602 7
603 8
604 8 L604V,
605 9 G605E,
606 10 A606T,
607 11 G607D, G607V, G607R,
608 11 D608H, D608N,
609 12
610 13 E610K,
611 13
612 14
613 14
614 15 P614S,