SCN5A Variant Q380H

Summary of observed carriers, functional annotations, and structural context for SCN5A Q380H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

20%

0/10 effective observations

Estimated BrS1 penetrance

39%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

Q380H has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 (%)
NA NA NA 0.811 56 24

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
Literature, cohort, and gnomAD – 0 0 0 0 –
Variant features alone – 15 12 0 3 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 Q380H.
Neighbour residue Distance (Å) Observed variants
328 15
333 11 c.998+5G>A, c.998+1G>A,
364 12
277 11
271 15 L271V,
1702 13
901 15 S901L, E901K,
326 10
276 7 L276Q, L276P,
363 15
387 14
348 7 P348A,
279 11
385 10 A385T,
355 11 F355I, F355C,
1687 12
278 10 H278R, H278D,
372 14
388 15 I388S,
356 15 D356N,
334 13 c.999-424_1338+81del,
1711 14 c.5131delG,
361 14
904 14 W904X,
332 12 A332T,
343 15
365 15
327 11
1706 12 Q1706H, Q1706H,
376 6 R376H, R376C,
384 8 S384T,
1688 14
354 10
329 14
1692 10
386 11 G386R, G386E, G386R,
378 8
349 8 D349N,
373 11
1712 14 G1712C, G1712S,
379 6
1703 14
272 11
341 14 C341Y,
274 12 G274C,
325 6 L325R,
900 14
392 14
324 8
321 15 S321Y,
389 12 Y389X, Y389H,
345 14
393 11
390 15
275 11 N275K, N275K,
383 7
280 12 C280Y,
323 10
347 10
382 8
351 12 G351S, G351V, G351D, G351C,
374 11 W374G,
1689 11 D1689N,
350 13 H350Q, H350Q,
367 12 R367H, R367C, R367L,
346 14 E346G, E346D, E346D, E346K, E346X,
344 14 A344S,
381 5 c.1140+1G>A, c.1141-3C>A,
1686 14
322 12
375 9
1691 11
352 14 Y352C,
368 13
380 0
268 14 G268S,
377 6
353 8 T353I,