ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1812_1813dup (p.Asp605fs)

dbSNP: rs764743402
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.