SCN5A Variant R1623X

Summary of observed carriers, functional annotations, and structural context for SCN5A R1623X. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

10%

1/21 effective observations

Estimated BrS1 penetrance

38%

7/21 effective observations

Total carriers

11

5 BrS1 · 0 LQT3 · 6 unaffected

R1623X has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 1 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 29 39

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
28069705 2017 1 0 0 1 ARVD
16325048 2005 1 0 1 0
14523039 2003 4 0 0 1 SSS
15840483 2005 5 0 2 0
22885917 2012 1 0 1 0
28341781 2017 1 0 1 0
20129283 2010 1 0 1 0
20129283 2010 1 0 1 0
29574140 2018 1 0 1 0
30059973 2018 1 1 0 0
Literature, cohort, and gnomAD – 11 6 0 5 –
Variant features alone – 15 12 1 2 – –

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)
28069705 2017 0
28552050 2017 0
16325048 2005 HEK 0
20384651 2010 0
14523039 2003 HEK-tSA201 0
20539757 2010
15840483 2005
22885917 2012
28341781 2017
20129283 2010
20129283 2010
29574140 2018
30059973 2018