Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000844683 | SCV000059061 | pathogenic | Hypertrophic cardiomyopathy | 2015-08-27 | criteria provided, single submitter | clinical testing | The p.Tyr525X variant in MYBPC3 has been reported in one individual with HCM (Bo rtot 2011) and has been identified by our laboratory in one Caucasian individual with HCM. It has not been identified in large population studies. This variant leads to a premature termination codon at position 525, which is predicted to l ead to a truncated or absent protein. Heterozygous loss of function of the MYBPC 3 gene is an established disease mechanism in individuals with HCM. In summary, the p.Tyr525X variant meets our criteria to be classified as pathogenic for HCM in an autosomal dominant manner based upon the predicted impact to the protein. |
| Blueprint Genetics | RCV000035413 | SCV000207040 | likely pathogenic | Primary familial hypertrophic cardiomyopathy | 2015-03-26 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000844683 | SCV002139023 | pathogenic | Hypertrophic cardiomyopathy | 2023-05-17 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 42547). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 21817903, 30775854). This sequence change creates a premature translational stop signal (p.Tyr525*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). |
| Ambry Genetics | RCV003372598 | SCV004084335 | pathogenic | Cardiovascular phenotype | 2023-07-24 | criteria provided, single submitter | clinical testing | The p.Y525* pathogenic mutation (also known as c.1575T>G), located in coding exon 17 of the MYBPC3 gene, results from a T to G substitution at nucleotide position 1575. This changes the amino acid from a tyrosine to a stop codon within coding exon 17. This mutation has been reported in multiple individuals with HCM (Bortot B et al. Diagn. Mol. Pathol., 2011 Sep;20:175-9; Walsh R et al. Genet. Med., 2017 02;19:192-203; Jääskeläinen P et al. ESC Heart Fail, 2019 Apr;6:436-445). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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. |