SCN5A Variant c.3045_3046delGA

Summary of observed carriers, functional annotations, and structural context for SCN5A c.3045_3046delGA. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

11%

0/11 effective observations

Estimated BrS1 penetrance

35%

3/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

c.3045_3046delGA has not been reported in gnomAD. This residue resides in a 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 38 14

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
19606473 2009 1 0 1 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)
19606473 2009

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.3045_3046delGA.
Neighbour residue Distance (Å) Observed variants
1001 15
1002 14 c.3005-3012delCCAGCTGG, P1002S,
1003 14
1004 13 C1004R,
1005 13 I1005T, I1005V,
1006 12 A1006S,
1007 11 T1007N, T1007I,
1008 11 P1008S,
1009 10
1010 9
1011 8 P1011L, P1011S,
1012 8
1013 7
1014 5 P1014S,
1015 4 p.G1015DfsX14, E1015K,
1016 0 c.3045_3046delGA, T1016M,
1017 4
1018 5 K1018E,
1019 7
1020 8
1021 8 P1021S,
1022 9
1023 10 R1023H, R1023P, R1023C,
1024 11 K1024R,
1025 11 E1025A,
1026 12
1027 13 R1027P, R1027Q, R1027W,
1028 13
1029 14 E1029K,
1030 14
1031 15 p.G1031fsX27,