SCN5A Variant G579R

Summary of observed carriers, functional annotations, and structural context for SCN5A G579R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

1/33 effective observations

Estimated BrS1 penetrance

3%

0/33 effective observations

Total carriers

23

0 BrS1 · 1 LQT3 · 22 unaffected

G579R is present in 21 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 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 (%)
-0.34 0.08 0.49 0.55 2 3

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
16414944 2005 1 1 0 0
20129283 2010 1 0 0 0
Literature, cohort, and gnomAD – 23 22 1 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)
16414944 2005
20129283 2010

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 G579R.
Neighbour residue Distance (Å) Observed variants
564 15
565 14
566 14
567 13 L567Q,
568 13 R568H, R568C,
569 12 c.1705dupC, R569W, R569Q,
570 11 T570N,
571 11 S571I,
572 10 A572S, A572D, A572V, A572F,
573 9 Q573X, Q573E, Q573R,
574 8 c.1721delG, G574E,
575 8
576 7
577 5 S577N,
578 4 P578R, P578T,
579 0 G579R, G579R,
580 4
581 5 S581L,
582 7
583 8 P583L,
584 8 G584R,
585 9
586 10 A586G, A586T, p.586_587delAL,
587 11
588 11 H588R, H588N,
589 12
590 13 K590Q,
591 13
592 14 N592K, N592S, N592K,
593 14
594 15