ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3102C>T (p.Ala1034=)

gnomAD frequency: 0.00058  dbSNP: rs200663253
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035560 SCV000059210 likely benign not specified 2015-11-19 criteria provided, single submitter clinical testing p.Ala1034Ala 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 sequence. It has been identified in 0.2% (26/11544) of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs200663253).
Ambry Genetics RCV000243240 SCV000318809 likely benign Cardiovascular phenotype 2020-03-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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 RCV001094055 SCV000372294 uncertain significance Hypertrophic cardiomyopathy 4 2018-01-13 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV000334330 SCV000372295 benign Left ventricular noncompaction 10 2018-01-13 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.
Invitae RCV000296162 SCV000558161 benign Hypertrophic cardiomyopathy 2024-02-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000777778 SCV000913751 benign Cardiomyopathy 2018-05-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000035560 SCV000919806 benign not specified 2018-09-17 criteria provided, single submitter clinical testing Variant summary: MYBPC3 c.3102C>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 variant allele was found at a frequency of 0.00067 in 273868 control chromosomes, predominantly at a frequency of 0.0033 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 3-folds higher than 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 Latino origin. To our knowledge, no occurrence of c.3102C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant twice as likely benign/bening and once as uncertain significance.Based on the evidence outlined above, the variant was classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000777778 SCV001333819 likely benign Cardiomyopathy 2017-12-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001705648 SCV001472986 likely benign not provided 2023-06-28 criteria provided, single submitter clinical testing
GeneDx RCV001705648 SCV001940800 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001705648 SCV002821622 likely benign not provided 2022-10-01 criteria provided, single submitter clinical testing MYBPC3: BP4, BP7
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001705648 SCV001930071 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001705648 SCV001972620 likely benign not provided no assertion criteria provided clinical testing

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