SCN5A Variant E867Q
Summary of observed carriers, functional annotations, and structural context for SCN5A E867Q. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/11 effective observations
Estimated BrS1 penetrance
40%
4/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -1.78 | 0.993 | -0.81 | 0.677 | 43 | 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 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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 |
|---|---|---|
| 880 | 13 | |
| 860 | 13 | p.L860fsx89, |
| 911 | 13 | G911E |
| 864 | 5 | |
| 870 | 11 | |
| 862 | 8 | |
| 867 | 0 | E867K, E867Q, E867X, |
| 859 | 13 | |
| 216 | 14 | S216X, S216L, |
| 871 | 13 | |
| 909 | 9 | |
| 858 | 14 | M858L, M858L, |
| 877 | 14 | |
| 869 | 7 | R869S, R869S, |
| 876 | 12 | |
| 905 | 15 | |
| 865 | 8 | |
| 857 | 15 | G857D, |
| 868 | 6 | c.2602delC, L868X, |
| 875 | 11 | |
| 882 | 11 | |
| 908 | 13 | |
| 863 | 5 | |
| 861 | 12 | p.F861WfsX90, c.2582_2583delTT, |
| 906 | 13 | |
| 881 | 13 | |
| 866 | 4 | S866P, S866L, |
| 874 | 14 | G874D, |
| 910 | 10 | S910L, |