SCN5A Variant G639R

Summary of observed carriers, functional annotations, and structural context for SCN5A G639R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

34%

2/13 effective observations

Estimated BrS1 penetrance

6%

0/13 effective observations

Total carriers

3

0 BrS1 · 2 LQT3 · 1 unaffected

G639R is present in 1 alleles 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 (%)
1.72 0.001 1.27 0.488 5 24

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
16922724 2006 1 1 0 0
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD – 3 1 2 0 –
Variant features alone – 15 15 0 0 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
19716085 2009
16922724 2006

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 G639R.
Neighbour residue Distance (Å) Observed variants
624 15 L624Q,
625 14 E625D, E625Q, c.1872dupA, E625D,
626 14
627 13 P627L,
628 13 P628R,
629 12 D629Y,
630 11 T630M,
631 11 p.T631VfsX101, c.1890+5G>A, c.1890G>A,
632 10 T632M,
633 9
634 8 S634L, S634W,
635 8
636 7 E636K,
637 5 P637L,
638 4 G638D,
639 0 G639R, G639A, G639R
640 4 P640L, P640A, P640S,
641 5
642 7
643 8
644 8
645 9
646 10 c.1936delC, p.Q646RfsX5,
647 11 A647S, A647D, A647V,
648 11 P648L,
649 12 C649R, C649Y,
650 13
651 13 c.1950_1953delAGAT, D651H,
652 14 G652D, G652S,
653 14
654 15 E654D, E654K, E654Q, E654X , E654D,