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

N275K has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-5.54 0.801 3.66 0.701 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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
18452873 2008
19716085 2009

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near N275K.
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 F355I, F355C,
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 Y389H, Y389X,
269 10
1620 12 T1620K, T1620M,
345 12
393 14
275 0 N275K, N275K,
383 12
280 13 C280Y,
323 14
347 11
382 11
1548 14 E1548K, G1548K,
351 14 G351S, G351C, G351D, G351V,
265 14 A265V,
1619 13 P1619Q, P1619L, c.4856delC,
342 11
1551 12 D1551N, D1551Y,
346 14 E346K, E346G, E346X, E346D, E346D,
344 10 A344S,
381 8 c.1140+1G>A, c.1141-3C>A,
380 11
268 9 G268S,
377 12
353 12 T353I,
1623 13 c.4867delC, R1623X, R1623Q, R1623L