SCN5A Variant D498G

Summary of observed carriers, functional annotations, and structural context for SCN5A D498G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

11%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

D498G 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 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 0.483 9 1

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 D498G.
Neighbour residue Distance (Å) Observed variants
483 15
484 14
485 14
486 13 T486S, T486A, T486S,
487 13
488 12
489 11
490 11 G490A, G490E,
491 10 E491G,
492 9
493 8 R493K,
494 8
495 7
496 5 K496N, K496N, K496M
497 4 S497C,
498 0
499 4
500 5 E500K,
501 7 D501G,
502 8
503 8 P503S,
504 9 R504T,
505 10 A505E,
506 11 M506K,
507 11 p.N507_L515dup,
508 12
509 13
510 13
511 14
512 14 T512I,
513 15 c.1537delC, R513H, R513C, R513P,