SCN5A Variant L325R
Summary of observed carriers, functional annotations, and structural context for SCN5A L325R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
5%
0/11 effective observations
Estimated BrS1 penetrance
62%
6/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.72 | 0.317 | -2.29 | 0.919 | 87 | 7 |
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 |
|---|---|---|---|---|---|---|---|
| 15890323 | 2005 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 10 | 0 | 5 | – | – |
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.
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 | 11 | |
| 333 | 9 | c.998+1G>A, c.998+5G>A |
| 277 | 10 | |
| 326 | 5 | |
| 276 | 7 | L276Q, L276P, |
| 387 | 15 | |
| 348 | 8 | P348A, |
| 279 | 6 | |
| 385 | 9 | A385T, |
| 355 | 14 | F355I, F355C, |
| 1687 | 14 | |
| 330 | 15 | S330F, |
| 278 | 6 | H278R, H278D, |
| 334 | 9 | c.999-424_1338+81del, |
| 332 | 9 | A332T, |
| 343 | 12 | |
| 327 | 7 | |
| 339 | 13 | |
| 376 | 11 | R376H, R376C, |
| 384 | 5 | S384T, |
| 354 | 12 | |
| 329 | 12 | |
| 1692 | 12 | |
| 386 | 11 | G386E, G386R, G386R, |
| 340 | 14 | R340Q, R340W, |
| 378 | 12 | |
| 331 | 14 | |
| 349 | 11 | D349N, |
| 379 | 9 | |
| 272 | 12 | |
| 341 | 9 | C341Y, |
| 274 | 11 | G274C, |
| 335 | 10 | C335S, C335R, C335S, |
| 325 | 0 | L325R, |
| 1690 | 14 | D1690N, c.5068_5070delGA, |
| 324 | 5 | |
| 321 | 12 | S321Y, |
| 389 | 14 | Y389X, Y389H, |
| 345 | 12 | |
| 275 | 9 | N275K, N275K, |
| 383 | 5 | |
| 280 | 7 | C280Y, |
| 323 | 6 | |
| 347 | 10 | |
| 382 | 9 | |
| 351 | 13 | G351D, G351S, G351C, G351V, |
| 320 | 14 | T320N, |
| 1689 | 11 | D1689N, |
| 350 | 15 | H350Q, H350Q, |
| 342 | 10 | |
| 346 | 12 | E346D, E346X, E346K, E346D, E346G, |
| 336 | 12 | P336L, |
| 344 | 10 | A344S, |
| 381 | 8 | c.1140+1G>A, c.1141-3C>A, |
| 322 | 10 | |
| 375 | 14 | |
| 1691 | 11 | |
| 380 | 6 | |
| 377 | 11 | |
| 281 | 11 | V281M, |
| 353 | 11 | T353I, |