ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2686G>A (p.Val896Met)

gnomAD frequency: 0.00601  dbSNP: rs35078470
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Total submissions: 24
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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 RCV000143915 SCV000051564 benign Primary familial hypertrophic cardiomyopathy 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035521 SCV000059171 benign not specified 2015-06-25 criteria provided, single submitter clinical testing p.Val896Met in exon 26 of MYBPC3: This variant is not expected to have clinical significance because it has been identified in 10% (68/690) of Finnish chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs35078470).
CSER _CC_NCGL, University of Washington RCV000204363 SCV000212192 likely benign Hypertrophic cardiomyopathy 2015-03-11 criteria provided, single submitter research
Eurofins Ntd Llc (ga) RCV000035521 SCV000228298 likely benign not specified 2015-05-15 criteria provided, single submitter clinical testing
Invitae RCV000204363 SCV000261462 benign Hypertrophic cardiomyopathy 2024-01-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000251320 SCV000318931 benign Cardiovascular phenotype 2016-06-06 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina RCV000602093 SCV000372318 likely benign Hypertrophic cardiomyopathy 4 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000602093 SCV000743549 likely benign Hypertrophic cardiomyopathy 4 2017-07-28 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000602093 SCV000744836 benign Hypertrophic cardiomyopathy 4 2015-09-21 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001705647 SCV000885759 benign not provided 2020-12-08 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000776054 SCV000910681 benign Cardiomyopathy 2018-03-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000035521 SCV000919804 benign not specified 2018-07-31 criteria provided, single submitter clinical testing Variant summary: MYBPC3 c.2686G>A (p.Val896Met) results in a conservative amino acid change located in the Fibronectin type III of the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0064 in 203838 control chromosomes in the gnomAD database, including 16 homozygotes. The observed variant frequency is more than 6-fold above the estimated maximal expected allele frequency for a pathogenic variant in MYBPC3 causing Hypertrophic Cardiomyopathy phenotype (0.001), strongly suggesting that the variant is benign. c.2686G>A has been reported in the literature in individuals affected with Hypertrophic Cardiomyopathy. These data do not allow any conclusion about variant significance. Co-occurrences with other pathogenic variants have been reported in multiple individuals tested at LCA (MYBPC3 c.2373dupG, p.Trp792fsX41; MYH7 c.428G>A, p.Arg143Gln), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000845297 SCV000987329 benign Primary familial dilated cardiomyopathy criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001106087 SCV001263120 benign Left ventricular noncompaction 10 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx RCV001705647 SCV001872136 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 27737317, 28798025, 27182706, 26332594, 26914223, 27153395, 25569433, 21310275, 25078086, 25637381, 10521296, 21472310, 12110947, 15010274, 25447171, 23299917, 22763267, 24888384, 24055113)
CeGaT Center for Human Genetics Tuebingen RCV001705647 SCV002544563 likely benign not provided 2024-04-01 criteria provided, single submitter clinical testing MYBPC3: BP4, BS2
Fulgent Genetics, Fulgent Genetics RCV002496532 SCV002805295 benign Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2022-04-05 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004549425 SCV004739628 likely benign MYBPC3-related disorder 2020-08-24 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Blueprint Genetics RCV000143915 SCV000188788 likely benign Primary familial hypertrophic cardiomyopathy 2014-06-26 no assertion criteria provided clinical testing
CSER _CC_NCGL, University of Washington RCV000143915 SCV000190370 likely benign Primary familial hypertrophic cardiomyopathy 2014-06-01 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000602093 SCV000733037 benign Hypertrophic cardiomyopathy 4 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000035521 SCV001919454 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000035521 SCV001956245 benign not specified no assertion criteria provided clinical testing
Cohesion Phenomics RCV000204363 SCV003800596 benign Hypertrophic cardiomyopathy 2022-10-10 no assertion criteria provided clinical testing

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