SCN5A Variant V396A
Summary of observed carriers, functional annotations, and structural context for SCN5A V396A. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
11%
0/11 effective observations
Estimated BrS1 penetrance
53%
5/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 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 (%) |
|---|---|---|---|---|---|
| -3.92 | 0.999 | -2.38 | 0.977 | 71 | 19 |
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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| 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) |
|---|---|---|---|---|---|---|
| 20129283 | 2010 |
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 |
|---|---|---|
| 403 | 10 | |
| 364 | 10 | |
| 271 | 13 | L271V, |
| 266 | 13 | L266H, |
| 363 | 13 | |
| 404 | 10 | L404V, L404Q, |
| 1627 | 14 | |
| 396 | 0 | V396L, V396A, |
| 1624 | 14 | V1624I, |
| 355 | 12 | F355I, F355C, |
| 391 | 10 | |
| 372 | 13 | |
| 401 | 7 | S401P, |
| 388 | 15 | I388S, |
| 371 | 9 | Q371E, |
| 361 | 12 | |
| 260 | 9 | |
| 366 | 10 | |
| 365 | 7 | |
| 1706 | 14 | Q1706H, Q1706H, |
| 258 | 14 | V258A, |
| 369 | 7 | M369K, |
| 1767 | 14 | Y1767C |
| 378 | 11 | |
| 402 | 9 | F402L, F402L, F402L, |
| 373 | 14 | |
| 267 | 9 | |
| 262 | 12 | S262G, |
| 256 | 14 | |
| 399 | 7 | |
| 272 | 12 | |
| 397 | 4 | I397V, I397F, I397T, |
| 405 | 12 | |
| 1657 | 15 | |
| 362 | 12 | |
| 261 | 9 | |
| 1709 | 12 | p.T1709del, T1709R, T1709M, |
| 1628 | 15 | |
| 392 | 6 | |
| 389 | 12 | Y389H, Y389X, |
| 269 | 14 | |
| 395 | 5 | |
| 393 | 6 | |
| 390 | 11 | |
| 394 | 7 | |
| 1658 | 15 | |
| 264 | 6 | |
| 1708 | 14 | T1708I, |
| 259 | 13 | |
| 382 | 14 | |
| 265 | 10 | A265V, |
| 374 | 10 | W374G, |
| 1705 | 12 | |
| 358 | 15 | |
| 367 | 11 | R367C, R367H, R367L, |
| 263 | 10 | V263I, |
| 370 | 10 | T370M, |
| 1661 | 15 | G1661R, G1661R, G1661E, |
| 381 | 13 | c.1140+1G>A, c.1141-3C>A, |
| 406 | 14 | N406S, N406K, N406K, |
| 368 | 5 | |
| 268 | 10 | G268S, |
| 377 | 11 | |
| 398 | 8 | |
| 257 | 12 | |
| 400 | 6 | G400R, G400R, G400E, G400A, |