SCN5A Variant c.2602delC

Summary of observed carriers, functional annotations, and structural context for SCN5A c.2602delC. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/12 effective observations

Estimated BrS1 penetrance

51%

6/12 effective observations

Total carriers

2

2 BrS1 · 0 LQT3 · 0 unaffected

c.2602delC has not been reported 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 59 1

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
20129283 2010 1 0 1 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 2 0 0 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)
20129283 2010
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 c.2602delC.
Neighbour residue Distance (Å) Observed variants
350 14 H350Q, H350Q,
880 13
911 11 G911E,
864 7
870 5
862 11
867 6 E867K, E867Q, E867X,
871 7
909 6
877 12
872 12 D872N,
869 6 R869S, R869S,
876 10
905 11
865 8
913 15
915 14 C915R
868 0 c.2602delC, L868X,
875 9
882 13
908 8
873 12 S873A,
863 10
912 14 Q912R,
861 13 p.F861WfsX90, c.2582_2583delTT,
906 11
881 13
866 7 S866P, S866L,
907 13
874 10 G874D,
910 9 S910L,