ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2997C>T (p.Gly999=) (rs377283955)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618610 SCV000736571 uncertain significance Cardiovascular phenotype 2017-06-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770329 SCV000901763 benign Cardiomyopathy 2017-10-30 criteria provided, single submitter clinical testing
GeneDx RCV000035547 SCV000170440 benign not specified 2013-06-12 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000035547 SCV000917814 likely benign not specified 2018-05-08 criteria provided, single submitter clinical testing Variant summary: MYBPC3 c.2997C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The observed variant frequency within African control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYBPC3 causing Hypertrophic Cardiomyopathy phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.2997C>T in individuals affected with Hypertrophic Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign (x2) and uncertain significance (x1). Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000232545 SCV000284236 likely benign Hypertrophic cardiomyopathy 2017-11-10 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035547 SCV000059197 likely benign not specified 2015-08-21 criteria provided, single submitter clinical testing p.Gly999Gly in exon 29 of MYBPC3: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus region. This variant has been identified in 0.1% (8/8424) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs377283955).

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