ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3491-2A>T (rs397516022)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000443859 SCV000516855 pathogenic not provided 2018-04-27 criteria provided, single submitter clinical testing The c.3491-2 A>T variant in the MYBPC3 gene has been reported previously in association with hypertrophic cardiomyopathy (HCM) (Alfares et al., 2015). This variant destroys the canonical splice acceptor site in intron 31 and is predicted to cause abnormal gene splicing. Other splice site variants in the MYBPC3 gene, including a different variant affecting the same acceptor site (c.3491-1 G>A), have been reported in Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014). Furthermore, the c.3491-2 A>T variant is not observed in large population cohorts (Lek et al., 2016).
Invitae RCV000464319 SCV000546428 likely pathogenic Hypertrophic cardiomyopathy 2016-07-01 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 31 of the MYBPC3 gene. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MYBPC3-related disease. ClinVar contains an entry for this variant (Variation ID: 42717). In summary, donor and acceptor splice site variants are typically truncating (PMID: 16199547), and truncating variants in MYBPC3 are known to be pathogenic (PMID: 19574547). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000464319 SCV000059243 pathogenic Hypertrophic cardiomyopathy 2012-04-18 criteria provided, single submitter clinical testing The 3491-2A>T variant (MYBPC3) has been identified in three individuals with HCM tested by our laboratory. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing lea ding to an abnormal or absent protein. Heterozygous loss of function of the MYBP C3 gene is an established disease mechanism in HCM. In summary, this variant mee ts our criteria for pathogenicity (

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