SCN5A Variant G1040R
Summary of observed carriers, functional annotations, and structural context for SCN5A G1040R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
5%
0/12 effective observations
Estimated BrS1 penetrance
5%
0/12 effective observations
Total carriers
2
0 BrS1 · 0 LQT3 · 2 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
---|---|---|---|---|---|
-0.4 | 0.005 | -1.15 | 0.49 | 2 | 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
Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
---|---|---|---|---|---|---|---|
20129283 | 2010 | 1 | 0 | 0 | 0 | ||
Literature, cohort, and gnomAD | – | 2 | 2 | 0 | 0 | – | |
Variant features alone | – | 15 | 15 | 0 | 0 | – | – |
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) |
---|---|---|---|---|---|---|
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.
Neighbour residue | Distance (Å) | Observed variants |
---|---|---|
1025 | 15 | E1025A, |
1026 | 14 | |
1027 | 14 | R1027P, R1027W, R1027Q, |
1028 | 13 | |
1029 | 13 | E1029K, |
1030 | 12 | |
1031 | 11 | p.G1031fsX27, |
1032 | 11 | E1032D, E1032D, E1032K, |
1033 | 10 | Q1033R, |
1034 | 9 | P1034T, |
1035 | 8 | G1035V, |
1036 | 8 | |
1037 | 7 | |
1038 | 5 | |
1039 | 4 | |
1040 | 0 | G1040R, G1040R, |
1041 | 4 | D1041N, D1041G, |
1042 | 5 | |
1043 | 7 | E1043K, |
1044 | 8 | |
1045 | 8 | V1045M, |
1046 | 9 | |
1047 | 10 | c.3140_3141dupTG, |
1048 | 11 | P1048S, c.3142_3143insTG, p.P1048SfsX96, |
1049 | 11 | |
1050 | 12 | A1050T, p.A1050DfsX9, p.A1050CfsX9, |
1051 | 13 | V1051A, |
1052 | 13 | p.A1052CfsX7, A1052D, |
1053 | 14 | E1053K, |
1054 | 14 | |
1055 | 15 | D1055G, |