SCN5A Variant c.3140_3141dupTG

Summary of observed carriers, functional annotations, and structural context for SCN5A c.3140_3141dupTG. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

44%

4/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

c.3140_3141dupTG 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 3 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 54 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
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD 1 0 0 1
Variant features alone 15 12 0 3

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

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.3140_3141dupTG.
Neighbour residue Distance (Å) Observed variants
1032 15 E1032D, E1032D, E1032K,
1033 14 Q1033R,
1034 14 P1034T,
1035 13 G1035V,
1036 13
1037 12
1038 11
1039 11
1040 10 G1040R, G1040R,
1041 9 D1041N, D1041G,
1042 8
1043 8 E1043K,
1044 7
1045 5 V1045M,
1046 4
1047 0 c.3140_3141dupTG,
1048 4 P1048S, c.3142_3143insTG, p.P1048SfsX96,
1049 5
1050 7 A1050T, p.A1050DfsX9, p.A1050CfsX9,
1051 8 V1051A,
1052 8 p.A1052CfsX7, A1052D,
1053 9 E1053K,
1054 10
1055 11 D1055G,
1056 11 T1056A,
1057 12
1058 13 c.3171_3172delTGinsA,
1059 13 Q1059X,
1060 14
1061 14 E1061D, E1061D,
1062 15 D1062H,