Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000598631 | SCV000710396 | pathogenic | not provided | 2018-01-19 | criteria provided, single submitter | clinical testing | Although the c.1812_1813dupCG pathogenic variant in the MYBPC3 gene has not been published in individuals with cardiomyopathy to our knowledge, this variant causes a shift in reading frame starting at codon aspartic acid 605, changing it to an alanine, and creating a premature stop codon at position 59 of the new reading frame, denoted p.Asp605AlafsX59. This 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. Multiple other frameshift variants in the MYBPC3 gene have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.1812_1813dupCG variant has not been observed at a significant frequency in large population cohorts (Kapplinger et al., 2014; Lek et al., 2016). |
Ambry Genetics | RCV002413686 | SCV002711953 | pathogenic | Cardiovascular phenotype | 2020-07-02 | criteria provided, single submitter | clinical testing | The c.1812_1813dupCG variant, located in coding exon 19 of the MYBPC3 gene, results from a duplication of CG at nucleotide position 1812, causing a translational frameshift with a predicted alternate stop codon (p.D605Afs*59). This variant was observed in an ostensibly healthy control subject from a hypertrophic cardiomyopathy (HCM) genetic testing cohort; however, clinical details were not provided for control participants (Kapplinger JD et al. J Cardiovasc Transl Res, 2014 Apr;7:347-61). 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. |