SCN5A Variant R535X
Summary of observed carriers, functional annotations, and structural context for SCN5A R535X. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
16%
2/23 effective observations
Estimated BrS1 penetrance
37%
8/23 effective observations
Total carriers
13
7 BrS1 · 1 LQT3 · 5 unaffected
Variant features alone are equivalent to phenotyping 1 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 | 1 | 50 |
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 |
|---|---|---|---|---|---|---|---|
| 25757662 | 2015 | 1 | 0 | 0 | 1 | SIDS | |
| 15890323 | 2005 | 1 | 0 | 1 | 0 | ||
| 19251209 | 2009 | 1 | 0 | 1 | 0 | ||
| 12106943 | 2002 | 1 | 0 | 1 | 0 | ||
| 16643399 | 2006 | 1 | 0 | 1 | 0 | ||
| 17404158 | 2007 | 1 | 0 | 1 | 0 | ||
| 20031634 | 2009 | 9 | 0 | 5 | 0 | ||
| 23631430 | 2013 | 1 | 1 | 0 | 0 | ||
| 26921764 | 2016 | 1 | 0 | 1 | 0 | ||
| 28361098 | 2017 | 3 | 0 | 0 | 3 | Conduction defects, Epilepsy | |
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 4 | 4 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 13 | 5 | 1 | 7 | – | |
| Variant features alone | – | 15 | 13 | 1 | 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) |
|---|---|---|---|---|---|---|
| 25757662 | 2015 | 0 | ||||
| 15890323 | 2005 | HEK | 0 | |||
| 19251209 | 2009 | |||||
| 12106943 | 2002 | |||||
| 16643399 | 2006 | |||||
| 17404158 | 2007 | |||||
| 20031634 | 2009 | |||||
| 23631430 | 2013 | |||||
| 26921764 | 2016 | |||||
| 28361098 | 2017 | |||||
| 20129283 | 2010 | |||||
| 20129283 | 2010 | |||||
| 20129283 | 2010 | |||||
| 20129283 | 2010 | |||||
| 29325976 | 2018 | |||||
| 30059973 | 2018 |