Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000412962 | SCV000491122 | pathogenic | not provided | 2016-12-02 | criteria provided, single submitter | clinical testing | The c.236dupA pathogenic variant in the MYBPC3 gene has previously been reported in association with HCM (Kapplinger et al., 2014). This variant causes a shift in reading frame at codon Tyrosine 79 and results in the creation of a premature stop codon, denoted p.Tyr79Ter. The c.236dupA pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. In addition, a different nucleotide change affecting the same residue (c.237 C>G) that also results in a stop codon at position 79 has been reported in the literature in association with severe HCM (Garcia-Pavia et al., 2007; Garcia-Pavia et al., 2011). Other downstream frameshift variants in the MYBPC3 gene have been reported in HGMD in association with cardiomyopathy (Stenson et al., 2014). Furthermore, the c.236dupA variant 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.In summary, c.236dupA in the MYBPC3 gene is interpreted as a pathogenic variant. |
| Ambry Genetics | RCV003372700 | SCV004094556 | pathogenic | Cardiovascular phenotype | 2023-08-09 | criteria provided, single submitter | clinical testing | The c.236dupA pathogenic mutation, located in coding exon 2 of the MYBPC3 gene, results from a duplication of A at nucleotide position 236, causing a translational frameshift with a predicted alternate stop codon (p.Y79*). This variant and a different nucleotide change resulting in the same protein impact (c.237C>G, p.Y79*) have been reported in individuals with hypertrophic cardiomyopathy (Millat G et al. Eur J Med Genet, 2010 Jul;53:261-7; Garcia-Pavia P et al. Eur J Heart Fail, 2011 Nov;13:1193-201; Berge KE et al. Clin Genet, 2014 Oct;86:355-60; Kapplinger JD et al. J Cardiovasc Transl Res, 2014 Apr;7:347-61). 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. |