SCN5A Variant D492H

Summary of observed carriers, functional annotations, and structural context for SCN5A D492H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/10 effective observations

Estimated BrS1 penetrance

6%

0/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

D492H has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 0.436 1 0

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 15 0 0 – –

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 D492H.
Neighbour residue Distance (Å) Observed variants
477 15 c.1428_1431delCAAG,
478 14
479 14
480 13 K480N, K480N
481 13 R481W, R481Q,
482 12 M482I, M482I, M482I,
483 11
484 11
485 10
486 9 T486S, T486A, T486S,
487 8
488 8
489 7
490 5 G490A, G490E,
491 4 E491G,
492 0
493 4 R493K,
494 5
495 7
496 8 K496N, K496N, K496M,
497 8 S497C,
498 9
499 10
500 11 E500K,
501 11 D501G,
502 12
503 13 P503S,
504 13 R504T,
505 14 A505E,
506 14 M506K,
507 15 p.N507_L515dup,