SCN5A Variant W822C
Summary of observed carriers, functional annotations, and structural context for SCN5A W822C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
12%
0/11 effective observations
Estimated BrS1 penetrance
56%
6/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -12.87 | 0.999 | -4.11 | 0.948 | 72 | 3 |
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 |
|---|---|---|---|---|---|---|---|
| 22840528 | 2012 | 1 | 0 | 1 | 0 | ||
| 24721456 | 2014 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 10 | 0 | 5 | – | – |
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.
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 |
|---|---|---|
| 723 | 13 | I723V, |
| 821 | 5 | |
| 1340 | 9 | V1340I, |
| 1339 | 7 | L1339F, p.L1339del |
| 721 | 12 | |
| 1344 | 12 | F1344S, F1344L, |
| 731 | 13 | T731I, |
| 819 | 6 | |
| 826 | 8 | N826D, |
| 726 | 15 | |
| 818 | 6 | |
| 825 | 6 | |
| 781 | 13 | W781X, |
| 720 | 13 | |
| 822 | 0 | W822X, W822C, |
| 830 | 15 | |
| 1346 | 13 | L1346I, L1346P, |
| 724 | 9 | T724I, |
| 1341 | 13 | |
| 728 | 11 | V728I, |
| 820 | 9 | |
| 823 | 6 | P823T, |
| 727 | 11 | |
| 827 | 11 | |
| 816 | 12 | F816L, F816Y, |
| 1338 | 13 | L1338V, |
| 817 | 10 | K817E, |
| 815 | 11 | |
| 1343 | 9 | |
| 1337 | 13 | |
| 1342 | 12 | |
| 725 | 13 | |
| 1347 | 14 | |
| 729 | 15 | p.L729del, |
| 1336 | 10 | |
| 824 | 6 | |
| 829 | 12 | |
| 1335 | 13 | M1335R, |
| 828 | 11 | L828V, |