SCN5A Variant R1629X

Summary of observed carriers, functional annotations, and structural context for SCN5A R1629X. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

14%

1/16 effective observations

Estimated BrS1 penetrance

38%

6/16 effective observations

Total carriers

6

2 BrS1 · 1 LQT3 · 3 unaffected

R1629X is present in 2 alleles in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 4 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 None 51 10

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
25829473 2015 2 0 1 0
27871843 2017 1 1 0 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD 6 3 1 2
Variant features alone 15 11 0 4

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)
25829473 2015 tsA201 0
30050137 2018 tsA201 2
27871843 2017
20129283 2010