SCN5A Variant G833R
Summary of observed carriers, functional annotations, and structural context for SCN5A G833R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/47 effective observations
Estimated BrS1 penetrance
3%
1/47 effective observations
Total carriers
37
0 BrS1 · 0 LQT3 · 37 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -7.83 | 1 | -3.45 | 0.959 | 9 | 18 |
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 |
|---|---|---|---|---|---|---|---|
| Literature, cohort, and gnomAD | – | 37 | 37 | 0 | 0 | – | |
| Variant features alone | – | 15 | 14 | 0 | 1 | – | – |
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) |
|---|---|---|---|---|---|---|
| 32533946 | 2020 | HEK | 109 | 1.3 | 2.2 |
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 |
|---|---|---|
| 937 | 12 | |
| 839 | 9 | L839P, |
| 842 | 14 | |
| 943 | 15 | S943N, |
| 780 | 13 | |
| 1344 | 15 | F1344S, F1344L, |
| 819 | 13 | |
| 836 | 5 | V836M, |
| 826 | 11 | N826D, |
| 234 | 14 | P234S, |
| 825 | 13 | |
| 934 | 14 | |
| 781 | 13 | W781X, |
| 944 | 15 | |
| 830 | 7 | |
| 833 | 0 | G833R, |
| 940 | 13 | S940N, |
| 831 | 6 | |
| 938 | 13 | |
| 840 | 11 | |
| 942 | 11 | |
| 843 | 14 | T843A, |
| 1456 | 13 | |
| 834 | 4 | N834D, |
| 827 | 11 | |
| 1460 | 12 | F1460L, |
| 816 | 14 | F816L, F816Y, |
| 837 | 8 | |
| 841 | 13 | p.N841TfsX2, N841K, |
| 941 | 10 | S941F, S941N, |
| 838 | 9 | |
| 824 | 15 | |
| 829 | 7 | |
| 832 | 4 | |
| 835 | 5 | S835A, S835L, |
| 828 | 9 | L828V, |