ClinVar Miner

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

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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
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).
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.
Invitae RCV001086680 SCV000218649 benign Hypertrophic cardiomyopathy 2020-12-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000035411 SCV000696315 benign not specified 2020-10-26 criteria provided, single submitter clinical testing Variant summary: MYBPC3 c.1564G>A (p.Ala522Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00044 in 250244 control chromosomes, predominantly at a frequency of 0.0039 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYBPC3 causing Cardiomyopathy phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1564G>A has been reported in the literature in individuals affected with Cardiomyopathy. These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Ambry Genetics RCV000620493 SCV000736329 likely benign Cardiovascular phenotype 2019-02-04 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;In silico models in agreement (benign);Other data supporting benign classification;Subpopulation frequency in support of benign classification
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
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000625025 SCV000743561 likely benign Familial hypertrophic cardiomyopathy 4 2014-10-09 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770363 SCV000901804 likely benign Cardiomyopathy 2015-12-22 criteria provided, single submitter clinical testing
Mendelics RCV000625025 SCV001138302 likely benign Familial hypertrophic cardiomyopathy 4 2019-05-28 criteria provided, single submitter clinical testing
Color Health, Inc RCV000770363 SCV001357308 likely benign Cardiomyopathy 2018-03-06 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148655 SCV000190371 likely benign Primary familial hypertrophic cardiomyopathy 2014-06-01 no assertion criteria provided research
Clinical Genetics,Academic Medical Center RCV000035411 SCV001919786 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000035411 SCV001953420 benign not specified no assertion criteria provided clinical testing

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