ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2920C>T (p.Gln974Ter)

dbSNP: rs727503180
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000844681 SCV000198831 pathogenic Hypertrophic cardiomyopathy 2013-04-30 criteria provided, single submitter clinical testing The Gln974X variant has been identified by our laboratory in 2 Caucasian individ uals with HCM (LMM unpublished data). This nonsense variant leads to a premature termination codon at position 974, which is predicted to lead to a truncated or absent protein. Truncating variants in MYBPC3 are a recognized pathogenic mecha nism for HCM. In summary, this variant meets our criteria to be classified as pa thogenic (http://pcpgm.partners.org/LMM) based upon the predicted impact to the protein.
GeneDx RCV000414556 SCV000490641 pathogenic not provided 2015-07-09 criteria provided, single submitter clinical testing The Q974X variant in the MYBPC3 gene has not been published as a pathogenic variant or as a benign polymorphism to our knowledge but has been reported as a pathogenic variant by two clinical laboratories (Landrum et al., 2014). Q974X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the MYBPC3 gene have been reported in HGMD in association with HCM(Stenson P et al., 2014). Furthermore, the Q974X variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore we interpret this variant as pathogenic.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV005400705 SCV000740365 pathogenic Cardiovascular phenotype 2024-03-27 criteria provided, single submitter clinical testing PVS1;PM2;PS4_supp;PP5
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798469 SCV002042183 pathogenic Cardiomyopathy 2022-12-14 criteria provided, single submitter clinical testing

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