SCN5A Variant K477E

Summary of observed carriers, functional annotations, and structural context for SCN5A K477E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/10 effective observations

Estimated BrS1 penetrance

42%

4/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

K477E has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 4 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 0.395 64 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 11 0 4

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 K477E.
Neighbour residue Distance (Å) Observed variants
462 15 E462K, E462A,
463 14 M463T, M463R,
464 14
465 13 p.P465LfsX5,
466 13 L466F, L466F,
467 12
468 11 P468L,
469 11 V469I,
470 10 N470K, N470K,
471 9
472 8
473 8 E473X,
474 7 R474G, R474K,
475 5 R475K, R475S, R475S,
476 4
477 0 c.1428_1431delCAAG,
478 4
479 5
480 7 K480N, K480N,
481 8 R481W, R481Q,
482 8 M482I, M482I, M482I,
483 9
484 10
485 11
486 11 T486A, T486S, T486S,
487 12
488 13
489 13
490 14 G490E, G490A,
491 14 E491G
492 15