SCN5A Variant E473D

Summary of observed carriers, functional annotations, and structural context for SCN5A E473D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/10 effective observations

Estimated BrS1 penetrance

11%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

E473D has not been reported 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 (%)
NA NA NA 0.212 11 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 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 E473D.
Neighbour residue Distance (Å) Observed variants
458 15 p.R458VfsX12, R458C, R458H
459 14 S459G,
460 14
461 13 L461V,
462 13 E462A, E462K,
463 12 M463R, M463T,
464 11
465 11 p.P465LfsX5,
466 10 L466F,
467 9
468 8 P468L,
469 8 V469I,
470 7 N470K,
471 5
472 4
473 0 E473X,
474 4 R474G, R474K,
475 5 R475K, R475S,
476 7
477 8 c.1428_1431delCAAG,
478 8
479 9
480 10 K480N,
481 11 R481Q, R481W,
482 11 M482I,
483 12
484 13
485 13
486 14 T486S, T486A,
487 14
488 15