SCN5A Variant A385T
Summary of observed carriers, functional annotations, and structural context for SCN5A A385T. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
13%
1/17 effective observations
Estimated BrS1 penetrance
13%
2/17 effective observations
Total carriers
7
0 BrS1 · 1 LQT3 · 6 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.96 | 0.997 | 1.63 | 0.784 | 29 | 9 |
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 |
|---|---|---|---|---|---|---|---|
| 27871843 | 2017 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 7 | 6 | 1 | 0 | – | |
| Variant features alone | – | 15 | 13 | 0 | 2 | – | – |
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) |
|---|---|---|---|---|---|---|
| 27871843 | 2017 |
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 | 9 | c.998+5G>A, c.998+1G>A, |
| 277 | 13 | |
| 271 | 9 | L271V, |
| 1702 | 12 | |
| 326 | 9 | |
| 276 | 8 | L276Q, L276P, |
| 387 | 8 | |
| 348 | 14 | P348A, |
| 270 | 14 | Q270K, |
| 279 | 13 | |
| 385 | 0 | A385T, |
| 355 | 12 | F355C, F355I, |
| 391 | 12 | |
| 330 | 9 | S330F, |
| 278 | 8 | H278R, H278D, |
| 388 | 7 | I388S, |
| 1698 | 14 | A1698T, |
| 334 | 10 | c.999-424_1338+81del, |
| 332 | 6 | A332T, |
| 343 | 13 | |
| 327 | 7 | |
| 384 | 4 | S384T, |
| 354 | 13 | |
| 329 | 6 | |
| 1692 | 13 | |
| 386 | 3 | G386R, G386R, G386E, |
| 378 | 10 | |
| 1699 | 14 | |
| 331 | 10 | |
| 267 | 14 | |
| 379 | 12 | |
| 272 | 8 | |
| 341 | 11 | C341Y, |
| 274 | 10 | G274C, |
| 273 | 13 | |
| 335 | 13 | C335S, C335S, C335R, |
| 325 | 9 | L325R, |
| 392 | 11 | |
| 324 | 13 | |
| 389 | 6 | Y389H, Y389X, |
| 269 | 15 | |
| 1620 | 12 | T1620K, T1620M, |
| 393 | 11 | |
| 390 | 11 | |
| 275 | 7 | N275K, N275K, |
| 383 | 8 | |
| 280 | 14 | C280Y, |
| 382 | 6 | |
| 1619 | 15 | c.4856delC, P1619Q, P1619L, |
| 1689 | 14 | D1689N, |
| 342 | 14 | |
| 381 | 6 | c.1140+1G>A, c.1141-3C>A, |
| 1691 | 11 | |
| 380 | 10 | |
| 268 | 12 | G268S, |
| 377 | 12 | |
| 1621 | 15 | |
| 353 | 15 | T353I, |