SCN5A Variant L276Q

Summary of observed carriers, functional annotations, and structural context for SCN5A L276Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/12 effective observations

Estimated BrS1 penetrance

64%

7/12 effective observations

Total carriers

2

2 BrS1 · 0 LQT3 · 0 unaffected

L276Q 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 5 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 (%)
-5.85 1 -3.49 0.997 82 10

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
17697823 2007 1 0 1 0
23321620 2013 1 0 1 0
28341781 2017 1 0 1 0
20129283 2010 1 0 1 0
29325976 2018 2 0 2 0
Literature, cohort, and gnomAD – 2 0 0 2 –
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.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
17697823 2007
23321620 2013
28341781 2017
20129283 2010
32533946 2020 HEK 1
29325976 2018

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 L276Q.
Neighbour residue Distance (Å) Observed variants
328 13
333 14 c.998+5G>A, c.998+1G>A,
364 11
277 6
271 11 L271V,
326 11
276 0 L276Q, L276P,
363 14
348 7 P348A,
270 13 Q270K,
360 12
279 9
385 8 A385T,
355 7 F355C, F355I,
1549 14
278 7 H278D, H278R,
388 15 I388S,
356 9 D356N,
334 15 c.999-424_1338+81del,
361 11
904 14 W904X,
332 13 A332T,
343 9
365 14
327 11
376 11 R376C, R376H,
384 6 S384T,
354 6
329 14
386 11 G386E, G386R,
378 12
349 11 D349N,
267 14
379 12
1550 11
357 12
272 6
341 12 C341Y,
274 5 G274C,
273 9
325 7 L325R,
392 13
324 11
321 15 S321Y,
389 11 Y389X, Y389H,
269 11
345 11
393 12
275 5 N275K,
383 10
280 13 C280Y,
323 11
347 7
382 10
351 10 G351S, G351V, G351C, G351D,
265 14 A265V,
374 14 W374G,
350 13 H350Q,
342 12
367 13 R367C, R367H, R367L,
1551 14 D1551Y, D1551N,
346 11 E346G, E346D, E346K, E346X,
359 14 p.A359PfsX12, A359T,
344 10 A344S,
381 6 c.1141-3C>A, c.1140+1G>A,
322 13
375 15
352 12 Y352C,
368 14
380 7
268 10 G268S,
377 8
353 7 T353I,