SCN5A Variant c.2320delT

Summary of observed carriers, functional annotations, and structural context for SCN5A c.2320delT. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

16%

0/11 effective observations

Estimated BrS1 penetrance

32%

3/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

c.2320delT 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 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 32 23

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
19251209 2009 1 0 1 0
21273195 2011 1 0 1 0
20129283 2010 2 0 2 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 13 0 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)
20129283 2010
19251209 2009
21273195 2011

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 c.2320delT.
Neighbour residue Distance (Å) Observed variants
774 0 p.Y774TfsX28, Y774D, Y774C, c.2320delT,
772 5 D772N,
767 14
770 12
775 6
771 10 L771V,
783 13 I783T,
769 12
773 4 P773S,
776 9 p.Y776del,
768 10
786 15
779 13 Q779X, Q779K,
777 8 F777L,
782 13 N782T,
778 9