Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Agnes Ginges Centre for Molecular Cardiology, |
RCV000201869 | SCV000256642 | pathogenic | Hypertrophic cardiomyopathy 1 | 2015-03-06 | criteria provided, single submitter | research | The MYBPC3 Tyr434* variant has been previously reported by Captur et al (2014) in one HCM proband. It is absent from the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). We have identified this variant in 1 HCM proband of Cyprian descent (IVS 24mm; PW 18mm). This variant is predicted to lead to a premature stop codon and result in a trauncated or absent protein. Loss-of-function mutations in the MYBPC3 gene are an established mechanism of disease in HCM. Hence, we classify MYBPC3 Tyr434* as "pathogenic". |
| Ambry Genetics | RCV002381693 | SCV002691184 | pathogenic | Cardiovascular phenotype | 2022-10-05 | criteria provided, single submitter | clinical testing | The p.Y434* pathogenic mutation (also known as c.1302C>A), located in coding exon 15 of the MYBPC3 gene, results from a C to A substitution at nucleotide position 1302. This changes the amino acid from a tyrosine to a stop codon within coding exon 15. This alteration has been reported in individuals with hypertrophic cardiomyopathy (HCM) (Captur G et al. Circ Cardiovasc Genet, 2014 Jun;7:241-8; Lopes LR et al. Heart, 2015 Feb;101:294-301; Bottillo I et al. Gene, 2016 Feb;577:227-35; Ross SB et al. Circ Cardiovasc Genet, 2017 Jun;10:[ePub ahead of print]). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |