SCN5A Variant N275K
Summary of observed carriers, functional annotations, and structural context for SCN5A N275K. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
27%
1/11 effective observations
Estimated BrS1 penetrance
22%
2/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 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 (%) |
---|---|---|---|---|---|
-5.54 | 0.801 | 3.66 | 0.699 | 34 | 2 |
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 |
---|---|---|---|---|---|---|---|
18452873 | 2008 | 2 | 1 | 0 | 1 | AF | |
19716085 | 2009 | 1 | 1 | 0 | 0 | ||
Literature, cohort, and gnomAD | – | 1 | 0 | 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.
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 | 10 | |
333 | 14 | c.998+1G>A, c.998+5G>A, |
364 | 14 | |
277 | 7 | |
271 | 8 | L271V, |
266 | 14 | L266H, |
326 | 11 | |
276 | 5 | L276Q, L276P, |
387 | 15 | |
348 | 12 | P348A, |
270 | 10 | Q270K, |
279 | 11 | |
385 | 7 | A385T, |
355 | 9 | F355C, F355I, |
1549 | 13 | |
330 | 15 | S330F, |
278 | 5 | H278D, H278R, |
388 | 13 | I388S, |
356 | 10 | D356N, |
334 | 14 | c.999-424_1338+81del, |
361 | 13 | |
332 | 12 | A332T, |
343 | 8 | |
327 | 9 | |
384 | 6 | S384T, |
354 | 9 | |
329 | 11 | |
386 | 10 | G386R, G386R, G386E, |
378 | 14 | |
267 | 13 | |
379 | 15 | |
1550 | 9 | |
357 | 13 | |
272 | 5 | |
341 | 10 | C341Y, |
274 | 4 | G274C, |
273 | 7 | |
325 | 9 | L325R, |
392 | 13 | |
324 | 14 | |
389 | 10 | Y389X, Y389H, |
269 | 10 | |
1620 | 12 | T1620M, T1620K |
345 | 12 | |
393 | 14 | |
275 | 0 | N275K, N275K, |
383 | 12 | |
280 | 13 | C280Y, |
323 | 14 | |
347 | 11 | |
382 | 11 | |
1548 | 14 | G1548K, E1548K, |
351 | 14 | G351C, G351S, G351D, G351V, |
265 | 14 | A265V, |
1619 | 13 | P1619L, c.4856delC, P1619Q, |
342 | 11 | |
1551 | 12 | D1551N, D1551Y, |
346 | 14 | E346G, E346K, E346X, E346D, E346D, |
344 | 10 | A344S, |
381 | 8 | c.1141-3C>A, c.1140+1G>A, |
380 | 11 | |
268 | 9 | G268S, |
377 | 12 | |
353 | 12 | T353I, |
1623 | 13 | R1623Q, c.4867delC, R1623L, R1623X, |