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
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico 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
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.
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 |