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
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico 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
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.
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.
Neighbour residue | Distance (Å) | Observed variants |
---|---|---|
1001 | 15 | |
1002 | 14 | c.3005-3012delCCAGCTGG, P1002S, |
1003 | 14 | |
1004 | 13 | C1004R, |
1005 | 13 | I1005V, I1005T, |
1006 | 12 | A1006S, |
1007 | 11 | T1007I, T1007N, |
1008 | 11 | P1008S, |
1009 | 10 | |
1010 | 9 | |
1011 | 8 | P1011S, P1011L, |
1012 | 8 | |
1013 | 7 | |
1014 | 5 | P1014S, |
1015 | 4 | E1015K, p.G1015DfsX14, |
1016 | 0 | T1016M, c.3045_3046delGA, |
1017 | 4 | |
1018 | 5 | K1018E, |
1019 | 7 | |
1020 | 8 | |
1021 | 8 | P1021S, |
1022 | 9 | |
1023 | 10 | R1023P, R1023H, R1023C, |
1024 | 11 | K1024R, |
1025 | 11 | E1025A, |
1026 | 12 | |
1027 | 13 | R1027P, R1027W, R1027Q, |
1028 | 13 | |
1029 | 14 | E1029K, |
1030 | 14 | |
1031 | 15 | p.G1031fsX27, |