Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158386 | SCV000208321 | pathogenic | not provided | 2016-03-30 | criteria provided, single submitter | clinical testing | The c.237delC mutation in MYBPC3 causes a shift in reading frame at codon Tyrosine 79, changing it to a premature Stop codon (Tyr79Stop). Although this mutation has not been reported previously to our knowledge, it is expected to result in an abnormal, truncated protein or in absence of protein from this allele due to mRNA decay. Also, this mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, a nucleotide substitution affecting this same residue (c.269 C>G) that also leads to the protein change Tyr79Stop has been reported in individuals with a severe presentation of HCM (Garcia-Pavia P et al., 2007). |
| Invitae | RCV000537938 | SCV000623552 | pathogenic | Hypertrophic cardiomyopathy | 2022-08-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr79*) 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). This variant is not present in population databases (gnomAD no frequency). A different variant (c.237C>A) giving rise to the same protein effect has been determined to be pathogenic (PMID: 23140321, 24510615). This suggests that this variant is also likely to be causative of disease. ClinVar contains an entry for this variant (Variation ID: 181091). For these reasons, this variant has been classified as Pathogenic. |