SCN5A Variant H508Q

Summary of observed carriers, functional annotations, and structural context for SCN5A H508Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

9%

0/10 effective observations

Estimated BrS1 penetrance

12%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

H508Q has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 0.478 11 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
Literature, cohort, and gnomAD – 0 0 0 0 –
Variant features alone – 15 14 0 1 – –

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 H508Q.
Neighbour residue Distance (Å) Observed variants
493 15 R493K,
494 14
495 14
496 13 K496M, K496N, K496N,
497 13 S497C,
498 12
499 11
500 11 E500K,
501 10 D501G,
502 9
503 8 P503S,
504 8 R504T,
505 7 A505E,
506 5 M506K,
507 4 p.N507_L515dup,
508 0
509 4
510 5
511 7
512 8 T512I,
513 8 R513C, c.1537delC, R513H, R513P,
514 9 G514C,
515 10
516 11
517 11 R517S, R517S,
518 12
519 13 S519F,
520 13 M520V, M520R,
521 14 K521E, c.1562delA,
522 14 P522S,
523 15 R523S, R523C, R523H