SCN5A Variant c.999-424_1338+81del
Summary of observed carriers, functional annotations, and structural context for SCN5A c.999-424_1338+81del. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
14%
0/12 effective observations
Estimated BrS1 penetrance
41%
4/12 effective observations
Total carriers
2
1 BrS1 · 0 LQT3 · 1 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 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 55 | 23 |
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 |
|---|---|---|---|---|---|---|---|
| 21288276 | 2011 | 2 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 2 | 1 | 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) |
|---|---|---|---|---|---|---|
| 21288276 | 2011 |
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 |
|---|---|---|
| 328 | 7 | |
| 333 | 3 | c.998+1G>A, c.998+5G>A, |
| 326 | 5 | |
| 276 | 15 | L276P, L276Q, |
| 387 | 12 | |
| 279 | 13 | |
| 385 | 10 | A385T, |
| 338 | 12 | |
| 330 | 9 | S330F, |
| 278 | 11 | H278R, H278D, |
| 388 | 15 | I388S, |
| 334 | 0 | c.999-424_1338+81del, |
| 332 | 5 | A332T, |
| 327 | 5 | |
| 339 | 10 | |
| 1688 | 15 | |
| 384 | 9 | S384T, |
| 1684 | 14 | W1684R, W1684R, |
| 329 | 8 | |
| 1692 | 12 | |
| 386 | 11 | G386E, G386R, G386R, |
| 340 | 12 | R340W, R340Q, |
| 1693 | 13 | |
| 1699 | 13 | |
| 331 | 8 | |
| 379 | 13 | |
| 341 | 9 | C341Y, |
| 335 | 4 | C335S, C335S, C335R, |
| 325 | 9 | L325R, |
| 1690 | 9 | D1690N, c.5068_5070delGA, |
| 324 | 10 | |
| 275 | 14 | N275K, N275K, |
| 383 | 7 | |
| 280 | 9 | C280Y, |
| 323 | 13 | |
| 382 | 11 | |
| 337 | 11 | |
| 1689 | 10 | D1689N, |
| 342 | 13 | |
| 336 | 7 | P336L, |
| 381 | 13 | c.1140+1G>A, c.1141-3C>A, |
| 1691 | 8 | |
| 380 | 13 | |
| 281 | 13 | V281M, |