SCN5A Variant E500K

Summary of observed carriers, functional annotations, and structural context for SCN5A E500K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/11 effective observations

Estimated BrS1 penetrance

14%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

E500K is present in 1 alleles in gnomAD. This residue resides in a Mild_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 (%)
-2.55 0.643 -0.13 0.506 16 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 – 1 1 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 E500K.
Neighbour residue Distance (Å) Observed variants
485 15
486 14 T486A, T486S, T486S,
487 14
488 13
489 13
490 12 G490E, G490A,
491 11 E491G,
492 11
493 10 R493K,
494 9
495 8
496 8 K496M, K496N, K496N,
497 7 S497C,
498 5
499 4
500 0 E500K,
501 4 D501G,
502 5
503 7 P503S,
504 8 R504T,
505 8 A505E,
506 9 M506K,
507 10 p.N507_L515dup,
508 11
509 11
510 12
511 13
512 13 T512I,
513 14 R513C, c.1537delC, R513H, R513P,
514 14 G514C
515 15