ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1351+1G>A (rs727503204)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208143 SCV000264052 likely pathogenic Primary familial hypertrophic cardiomyopathy 2015-05-04 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000151139 SCV000900734 pathogenic Cardiomyopathy 2016-12-28 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000614620 SCV000733053 pathogenic Familial hypertrophic cardiomyopathy 4 no assertion criteria provided clinical testing
Invitae RCV000464484 SCV000546488 likely pathogenic Hypertrophic cardiomyopathy 2018-11-08 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 15 of the MYBPC3 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals affected with hypertrophic cardiomyopathy (PMID: 20031602, 27532257) and in an individual affected with dilated cardiomyopathy (PMID: 21750094). ClinVar contains an entry for this variant (Variation ID: 164119). In summary, donor and acceptor splice site variants are typically loss-of-function (PMID: 16199547), and loss-of-function 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 RCV000844684 SCV000198923 pathogenic Primary dilated cardiomyopathy; Hypertrophic cardiomyopathy 2014-06-27 criteria provided, single submitter clinical testing The 1351+1G>A variant in MYBPC3 has been reported in 1 Caucasian adult with HCM, 1 Caucasian adult with DCM, and 1 Chinese adult with HCM, and segregated with d isease in 4 affected relatives from two families with HCM (Waldmuller 2001, Zou 2006 abstract, Ho 2009 and LMM unpublished data). It was absent from large popul ation studies. This variant occurs in the invariant region (+/- 1,2) of the spli ce consensus sequence and is predicted to cause altered splicing leading to an a bnormal or absent protein. In summary, this variant meets our criteria to be cla ssified as pathogenic (http://pcpgm.partners.org/LMM) based upon predicted funct ional effect, segregation studies, and absence from controls.

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