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, |