ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1564G>A (p.Ala522Thr) (rs11570082)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000620493 SCV000736329 likely benign Cardiovascular phenotype 2017-12-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,In silico models in agreement (benign),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Other data supporting benign classification
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000148655 SCV000054768 likely benign Primary familial hypertrophic cardiomyopathy 2013-06-24 criteria provided, single submitter research
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770363 SCV000901804 likely benign Cardiomyopathy 2015-12-22 criteria provided, single submitter clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148655 SCV000190371 likely benign Primary familial hypertrophic cardiomyopathy 2014-06-01 no assertion criteria provided research
GeneDx RCV000035411 SCV000207987 likely benign not specified 2018-01-17 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.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000625025 SCV000743561 likely benign Familial hypertrophic cardiomyopathy 4 2014-10-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589753 SCV000696315 likely benign not provided 2016-04-07 criteria provided, single submitter clinical testing Variant summary: The MYBPC3 c.1564G>A variant affects a non-conserved nucleotide, resulting in amino acid change from a non-polar Ala to a polar Thr. 3/5 in-silico tools predict this variant to be benign, but these in silico predictions have not been verified with functional studies. This variant was found in 50/121450 control chromosomes at a frequency of 0.0004117, which does not significantly exceed maximal expected frequency of a pathogenic MYBPC3 allele (0.0010005). However, the variant is predominantly found in Africans, with an allele frequency of 31/9788 African ExAC chromosomes (0.003167), which is 3-fold greater than the maximal expected pathogenic allele frequency, suggesting this missense mutation is a benign polymorphism in Africans. Although the variant has been reported in cardiomyopathy patients in the literature, none of these reports supply co-segregation data to confirm its association with the cardiomyopathy phenotype. Additionally, the variant has been classified as likely benign by multiple clinical laboratories. Taken together, the variant was classified as likely benign.
Invitae RCV000167998 SCV000218649 benign Hypertrophic cardiomyopathy 2017-09-27 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035411 SCV000059059 likely benign not specified 2012-05-22 criteria provided, single submitter clinical testing p.Ala522Thr in exon 17 of MYBPC3: This variant is not expected to have clinical significance, despite being reported in 2 individuals with HCM (Cardim 2005, Oli votto 2008), because it has been identified in 0.3% (31/9788) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs11570082).
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000035411 SCV000740367 likely benign not specified 2017-05-18 criteria provided, single submitter clinical testing

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