SCN5A Variant A332T
Summary of observed carriers, functional annotations, and structural context for SCN5A A332T. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
27%
2/13 effective observations
Estimated BrS1 penetrance
15%
1/13 effective observations
Total carriers
3
0 BrS1 · 1 LQT3 · 2 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 (%) |
|---|---|---|---|---|---|
| -3.13 | 0.271 | -0.15 | 0.681 | 25 | 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 |
|---|---|---|---|---|---|---|---|
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 2 | 1 | 0 | – | |
| 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) |
|---|---|---|---|---|---|---|
| 30059973 | 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 |
|---|---|---|
| 328 | 7 | |
| 333 | 3 | c.998+1G>A, c.998+5G>A, |
| 1702 | 11 | |
| 326 | 7 | |
| 276 | 13 | L276Q, L276P, |
| 387 | 7 | |
| 279 | 14 | |
| 385 | 6 | A385T, |
| 330 | 6 | S330F, |
| 278 | 11 | H278D, H278R, |
| 388 | 9 | I388S, |
| 1698 | 12 | A1698T |
| 334 | 5 | c.999-424_1338+81del, |
| 332 | 0 | A332T, |
| 327 | 6 | |
| 1695 | 15 | Q1695X, |
| 384 | 6 | S384T, |
| 1688 | 15 | |
| 329 | 4 | |
| 1692 | 10 | |
| 386 | 5 | G386R, G386R, G386E, |
| 1693 | 12 | |
| 378 | 12 | |
| 1699 | 11 | |
| 331 | 5 | |
| 379 | 11 | |
| 1703 | 15 | |
| 272 | 14 | |
| 341 | 11 | C341Y, |
| 335 | 9 | C335S, C335R, C335S, |
| 325 | 9 | L325R, |
| 1690 | 11 | c.5068_5070delGA, D1690N, |
| 324 | 12 | |
| 1697 | 15 | |
| 389 | 10 | Y389H, Y389X, |
| 393 | 15 | |
| 390 | 13 | |
| 275 | 12 | N275K, N275K, |
| 383 | 6 | |
| 280 | 12 | C280Y, |
| 323 | 15 | |
| 382 | 7 | |
| 1696 | 13 | |
| 1689 | 10 | D1689N, |
| 342 | 15 | |
| 336 | 12 | P336L, |
| 381 | 9 | c.1140+1G>A, c.1141-3C>A, |
| 1691 | 7 | |
| 380 | 12 |