SCN5A Variant R282H
Summary of observed carriers, functional annotations, and structural context for SCN5A R282H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/18 effective observations
Estimated BrS1 penetrance
46%
8/18 effective observations
Total carriers
8
4 BrS1 · 0 LQT3 · 4 unaffected
Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.53 | 1 | -0.88 | 0.794 | 54 | 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 |
|---|---|---|---|---|---|---|---|
| 15828879 | 2005 | 3 | 0 | 3 | 0 | ||
| 11901046 | 2002 | 1 | 0 | 1 | 0 | ||
| 20219395 | 2011 | 1 | 0 | 1 | 0 | ||
| 20625312 | 2010 | 1 | 0 | 1 | 0 | ||
| 28341781 | 2017 | 3 | 0 | 3 | 0 | ||
| 29574140 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 8 | 4 | 0 | 4 | – | |
| Variant features alone | – | 15 | 11 | 0 | 4 | – | – |
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) |
|---|---|---|---|---|---|---|
| 16864729 | 2006 | HEK | 0 | |||
| 21840964 | 2011 | HEK | 3 | |||
| 15828879 | 2005 | HEK | 12 | 5 | 5.3 | |
| 11901046 | 2002 | |||||
| 20219395 | 2011 | |||||
| 20625312 | 2010 | |||||
| 28341781 | 2017 | |||||
| 16880338 | 2006 | |||||
| 29574140 | 2018 |
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 |
|---|---|---|
| 287 | 12 | |
| 341 | 12 | C341Y, |
| 342 | 11 | |
| 326 | 13 | |
| 335 | 11 | C335S, C335R, C335S, |
| 339 | 5 | |
| 319 | 8 | G319S, G319R, G319C, |
| 317 | 14 | K317E, K317M, K317N, K317N, |
| 284 | 6 | |
| 336 | 9 | P336L, |
| 282 | 0 | R282C, R282H, |
| 279 | 12 | |
| 324 | 14 | |
| 321 | 11 | S321Y, |
| 344 | 14 | A344S |
| 340 | 9 | R340W, R340Q, |
| 285 | 6 | T285K, |
| 338 | 6 | |
| 322 | 14 | |
| 280 | 8 | C280Y, |
| 318 | 12 | |
| 281 | 6 | V281M, |
| 323 | 11 | |
| 283 | 6 | |
| 337 | 10 | |
| 286 | 8 | A286S, A286V, |
| 320 | 9 | T320N, |