SCN5A Variant V281M
Summary of observed carriers, functional annotations, and structural context for SCN5A V281M. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/13 effective observations
Estimated BrS1 penetrance
34%
4/13 effective observations
Total carriers
3
1 BrS1 · 0 LQT3 · 2 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 (%) |
|---|---|---|---|---|---|
| -1.52 | 0.999 | -1.44 | 0.724 | 50 | 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 |
|---|---|---|---|---|---|---|---|
| 24775617 | 2013 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 2 | 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) |
|---|---|---|---|---|---|---|
| 24775617 | 2013 |
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 |
|---|---|---|
| 343 | 11 | |
| 328 | 13 | |
| 277 | 13 | |
| 341 | 7 | C341Y, |
| 274 | 15 | G274C, |
| 342 | 5 | |
| 326 | 9 | |
| 335 | 10 | C335S, C335R, C335S, |
| 327 | 11 | |
| 339 | 6 | |
| 346 | 13 | E346K, E346G, E346X, E346D, E346D, |
| 319 | 8 | G319S, G319R, G319C, |
| 384 | 14 | S384T |
| 325 | 11 | L325R, |
| 348 | 15 | P348A, |
| 317 | 11 | K317E, K317M, K317N, K317N, |
| 284 | 10 | |
| 336 | 10 | P336L, |
| 282 | 6 | R282C, R282H, |
| 279 | 6 | |
| 324 | 11 | |
| 321 | 9 | S321Y, |
| 344 | 8 | A344S, |
| 340 | 6 | R340W, R340Q, |
| 338 | 8 | |
| 285 | 11 | T285K, |
| 345 | 10 | |
| 322 | 12 | |
| 278 | 10 | H278D, H278R, |
| 334 | 13 | c.999-424_1338+81del, |
| 383 | 14 | |
| 280 | 5 | C280Y, |
| 318 | 11 | |
| 281 | 0 | V281M, |
| 323 | 9 | |
| 347 | 15 | |
| 283 | 6 | |
| 337 | 13 | |
| 286 | 14 | A286S, A286V, |
| 320 | 7 | T320N, |