SCN5A Variant R222X
Summary of observed carriers, functional annotations, and structural context for SCN5A R222X. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
2/63 effective observations
Estimated BrS1 penetrance
57%
35/63 effective observations
Total carriers
53
33 BrS1 · 1 LQT3 · 19 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 28 | 30 |
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 |
|---|---|---|---|---|---|---|---|
| 27287068 | 2016 | 2 | 0 | 2 | 0 | ||
| 22277643 | 2012 | 38 | 0 | 25 | 0 | ||
| 26173111 | 2015 | 1 | 0 | 1 | 0 | ||
| 26467377 | 2016 | 7 | 0 | 1 | 0 | ||
| 27232914 | 2016 | 1 | 0 | 1 | 0 | ||
| 19716085 | 2009 | 1 | 1 | 0 | 0 | ||
| 20129283 | 2010 | 4 | 0 | 4 | 0 | ||
| 29325976 | 2018 | 2 | 0 | 2 | 0 | ||
| Literature, cohort, and gnomAD | – | 53 | 19 | 1 | 33 | – | |
| Variant features alone | – | 15 | 12 | 1 | 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.