SCN5A Variant K521E

Summary of observed carriers, functional annotations, and structural context for SCN5A K521E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/12 effective observations

Estimated BrS1 penetrance

21%

2/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

K521E is present in 2 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 2 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 (%)
-1.36 0.09 -1.11 0.552 33 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 – 2 2 0 0 –
Variant features alone – 15 13 0 2 – –

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 K521E.
Neighbour residue Distance (Å) Observed variants
506 15 M506K,
507 14 p.N507_L515dup,
508 14
509 13
510 13
511 12
512 11 T512I,
513 11 R513C, c.1537delC, R513H, R513P,
514 10 G514C,
515 9
516 8
517 8 R517S, R517S,
518 7
519 5 S519F,
520 4 M520V, M520R,
521 0 K521E, c.1562delA,
522 4 P522S,
523 5 R523S, R523C, R523H,
524 7 c.1570_1571insG, S524Y,
525 8 S525G,
526 8 R526C, R526H,
527 9 G527R, G527R,
528 10 S528R, S528R, S528R,
529 11
530 11 F530V, F530S,
531 12 T531A, T531I,
532 13 F532L, F532C, F532L, F532L,
533 13 R533S, R533C, R533H,
534 14
535 14 R535G, R535X, R535Q,
536 15 D536H