ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.237C>A (p.Tyr79Ter)

dbSNP: rs730880698
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000460781 SCV000546476 pathogenic Hypertrophic cardiomyopathy 2024-05-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr79*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 19574547, 23140321, 24510615). ClinVar contains an entry for this variant (Variation ID: 407333). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000483607 SCV000573944 pathogenic not provided 2017-03-14 criteria provided, single submitter clinical testing The Y79X (c.237 C>A) variant in the MYBPC3 gene has been reported in at least 3 individuals with confirmedhypertrophic cardiomyopathy (HCM) or who were referred for HCM gene testing (Kapplinger et al., 2014; Bos et al.,2014). This variant is predicted to cause loss of normal protein function either by protein truncation or nonsensemediatedmRNA decay. Other nonsense variants in the MYBPC3 gene, including a different nonsense variant at thesame residue (c.237 C>G), have been reported in Human Gene Mutation Database in association with HCM (Stensonet al., 2014), indicating that loss of function is a known disease mechanism. Finally, the Y79X (c.237 C>A) variantis not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome VariantServer).

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