Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158436 | SCV000208371 | likely pathogenic | not provided | 2012-01-20 | criteria provided, single submitter | clinical testing | This variant is denoted c.1685 C>A at the cDNA level or p.Ala562Glu (A562E) at the protein level. The Ala562Glu variant in the MYBPC3 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Ala562Glu is a non-conservative amino acid substitution of a neutral, non-polar Alanine with a negatively charged Glutamic acid at a residue that is conserved across species. In silico analysis predicts the Ala562Glu variant is probably damaging to protein structure or function. A mutation in a nearby codon (Cys566Arg) has been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. The NHLBI ESP Exome Variant Server reports Ala562Glu was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Therefore, with the clinical and molecular information available at this time, we cannot unequivocally determine the clinical significance of the Ala562Glu variant in MYBPC3, although the evidence suggests it is likely disease-causing. The variant is found in HCM panel(s). |
| Color Diagnostics, |
RCV003531995 | SCV004358715 | uncertain significance | Cardiomyopathy | 2022-11-21 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with glutamic acid at codon 562 of the MYBPC3 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYBPC3-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |