SCN5A Variant H278D

Summary of observed carriers, functional annotations, and structural context for SCN5A H278D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/11 effective observations

Estimated BrS1 penetrance

62%

6/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

H278D 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 (%)
-2.71 0.454 -2 0.83 90 3

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
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.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
20129283 2010

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 H278D.
Neighbour residue Distance (Å) Observed variants
328 8
333 11 c.998+5G>A, c.998+1G>A,
277 7
271 13 L271V,
326 7
276 7 L276Q, L276P,
348 11 P348A,
279 6
385 8 A385T,
355 13 F355I, F355C,
330 14 S330F,
278 0 H278R, H278D,
356 13 D356N,
334 11 c.999-424_1338+81del,
332 11 A332T,
343 6
327 6
339 14
384 5 S384T,
354 11
329 11
386 11 G386E, G386R, G386R
340 11 R340W, R340Q,
349 15 D349N,
379 15
1550 11
272 10
341 5 C341Y,
274 6 G274C,
273 11
335 11 C335R, C335S, C335S,
325 6 L325R,
324 11
321 13 S321Y,
269 15
389 13 Y389X, Y389H,
345 10
275 5 N275K, N275K,
383 10
280 8 C280Y,
323 10
347 10
382 12
351 14 G351D, G351S, G351V, G351C,
320 13 T320N,
342 6
1551 13 D1551Y, D1551N,
346 12 E346D, E346K, E346G, E346D, E346X,
336 14 P336L,
344 7 A344S,
381 10 c.1141-3C>A, c.1140+1G>A,
322 14
380 10
268 14 G268S,
377 14
281 10 V281M,
353 13 T353I,