SCN5A Variant M463R

Summary of observed carriers, functional annotations, and structural context for SCN5A M463R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/12 effective observations

Estimated BrS1 penetrance

4%

0/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

M463R is present in 2 alleles 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 0 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 (%)
-1.69 0.29 0.46 0.575 1 10

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 15 0 0 – –

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 M463R.
Neighbour residue Distance (Å) Observed variants
448 15
449 14 T449A, Y449C,
450 14
451 13
452 13 G452D,
453 12 V453M,
454 11
455 11
456 10 V456M,
457 9
458 8 R458C, p.R458VfsX12, R458H,
459 8 S459G,
460 7
461 5 L461V,
462 4 E462K, E462A,
463 0 M463R, M463T,
464 4
465 5 p.P465LfsX5,
466 7 L466F, L466F,
467 8
468 8 P468L,
469 9 V469I,
470 10 N470K, N470K,
471 11
472 11
473 12 E473X,
474 13 R474K, R474G,
475 13 R475S, R475S, R475K,
476 14
477 14 c.1428_1431delCAAG,
478 15