ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3253G>T (p.Glu1085Ter) (rs397516010)

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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, Partners HealthCare Personalized Medicine RCV000690167 SCV000059219 pathogenic Hypertrophic cardiomyopathy 2010-07-15 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000208092 SCV000264040 likely pathogenic Primary familial hypertrophic cardiomyopathy 2015-09-10 criteria provided, single submitter clinical testing
GeneDx RCV000255392 SCV000321912 pathogenic not provided 2018-06-11 criteria provided, single submitter clinical testing The E1085X variant in the MYBPC3 gene has not been reported as a pathogenic variant or as a benign variant to our knowledge. However, according to ClinVar this variant has been classified as pathogenic by another clinical laboratory (Landrum et al., 2014). E1085X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other downstream nonsense variants in the MYBPC3 gene have been reported in HGMD in association with HCM (Stenson et al., 2014). Furthermore, the E1085X pathogenic variant was not observed in approximately 6,100 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, E1085X in the MYBPC3 gene is interpreted as a pathogenic variant.
Invitae RCV000690167 SCV000817845 pathogenic Hypertrophic cardiomyopathy 2020-10-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1085*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with hypertrophic cardiomyopathy (PMID: 25611685, 27532257). ClinVar contains an entry for this variant (Variation ID: 42696). Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). For these reasons, this variant has been classified as Pathogenic.

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