SCN5A Variant c.3142_3143insTG

Summary of observed carriers, functional annotations, and structural context for SCN5A c.3142_3143insTG. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/12 effective observations

Estimated BrS1 penetrance

38%

4/12 effective observations

Total carriers

2

2 BrS1 · 0 LQT3 · 0 unaffected

c.3142_3143insTG has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_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 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
19251209 2009 1 0 1 0
21273195 2011 2 0 2 0
Literature, cohort, and gnomAD – 2 0 0 2 –
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)
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.3142_3143insTG.
Neighbour residue Distance (Å) Observed variants
1033 15 Q1033R,
1034 14 P1034T,
1035 14 G1035V,
1036 13
1037 13
1038 12
1039 11
1040 11 G1040R, G1040R,
1041 10 D1041N, D1041G,
1042 9
1043 8 E1043K,
1044 8
1045 7 V1045M,
1046 5
1047 4 c.3140_3141dupTG,
1048 0 c.3142_3143insTG, p.P1048SfsX96, P1048S,
1049 4
1050 5 p.A1050DfsX9, A1050T, p.A1050CfsX9,
1051 7 V1051A,
1052 8 A1052D, p.A1052CfsX7
1053 8 E1053K,
1054 9
1055 10 D1055G,
1056 11 T1056A,
1057 11
1058 12 c.3171_3172delTGinsA,
1059 13 Q1059X,
1060 13
1061 14 E1061D, E1061D,
1062 14 D1062H,
1063 15 E1063G,