SCN5A Variant W156X

Summary of observed carriers, functional annotations, and structural context for SCN5A W156X. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/13 effective observations

Estimated BrS1 penetrance

30%

3/13 effective observations

Total carriers

3

2 BrS1 · 0 LQT3 · 1 unaffected

W156X 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 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 (%)
NA NA NA None 6 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
27784737 2016 1 0 1 0
12574143 2003 2 0 0 1 DCM, conduction
19251209 2009 1 0 1 0
16764707 2006 1 0 1 0
21273195 2011 1 0 1 0
22885917 2012 2 0 2 0
20129283 2010 1 0 1 0
30059973 2018 1 1 0 0
Literature, cohort, and gnomAD 3 1 0 2
Variant features alone 15 14 0 1

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)
27784737 2016 hiPSC 0
12574143 2003 Xeno 0
19251209 2009
16764707 2006
21273195 2011
22885917 2012
20129283 2010
30059973 2018