ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1168del (p.His390fs) (rs397515889)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000844685 SCV000059021 pathogenic Hypertrophic cardiomyopathy 2010-04-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000035373 SCV000917813 pathogenic Primary familial hypertrophic cardiomyopathy 2018-04-30 criteria provided, single submitter clinical testing Variant summary: MYBPC3 c.1168delC (p.His390MetfsX16) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Phe412X and p.Pro453fsX21). The variant was absent in 242438 control chromosomes. c.1168delC has been reported in the literature in individuals affected with Hypertrophic Cardiomyopathy. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV000158489 SCV000208424 not provided not provided no assertion provided clinical testing The c.1168delC variant in MYBPC3 has been reported previously in an affected individual with cardiomyopathy (Erdmann et al., 2001). It causes a shift in reading frame beginning with Histidine codon 390, changing it to a Methionine, and creating a premature Stop codon at position 16 of the new reading frame (p. His390MetfsX16). This deletion is expected to result in absence of protein from this allele due to mRNA decay or in an abnormal, truncated protein that has lost its protein's titin and myosin-binding site (Erdmann et al., 2001).

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