ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1246G>A (p.Gly416Ser)

gnomAD frequency: 0.00046  dbSNP: rs371513491
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Total submissions: 10
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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 RCV000035380 SCV000059028 uncertain significance not specified 2016-04-14 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV001698949 SCV000208005 uncertain significance not provided 2022-12-06 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21310275, 24503780, 25637381, 21415409, 16858239, 22958901, 25351510, 15519027, 23299917, 28166811, 27532257, 27841901, 15563892, 30847666, 35130036, 35284542)
Invitae RCV000226889 SCV000284208 likely benign Hypertrophic cardiomyopathy 2024-01-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621944 SCV000736573 likely benign Cardiovascular phenotype 2023-03-17 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000625310 SCV000744855 uncertain significance Hypertrophic cardiomyopathy 4 2017-05-31 criteria provided, single submitter clinical testing
Mendelics RCV000625310 SCV001138307 benign Hypertrophic cardiomyopathy 4 2019-05-28 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001184758 SCV001350819 uncertain significance Cardiomyopathy 2022-12-01 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 416 of the MYBPC3 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional assays have not been performed for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 15519027, 15563892, 27841901), in individuals affected with dilated cardiomyopathy (PMID: 24503780, 35284542, 36166435), as well as in two unaffected individuals (PMID: 15519027). This variant has also been identified in 29/274848 chromosomes (24/23472 African chromosomes) in the general population by the Genome Aggregation Database (gnomAD). The relatively high frequency of this variant in the general population suggests that this variant is unlikely to be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health RCV000226889 SCV004834654 uncertain significance Hypertrophic cardiomyopathy 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 416 of the MYBPC3 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, PMID: 27666373). To our knowledge, functional assays have not been performed for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 15519027, 15563892, 27841901), in individuals affected with dilated cardiomyopathy (PMID: 24503780, 35284542, 36166435), as well as in two unaffected individuals (PMID: 15519027). This variant has also been identified in 29/274848 chromosomes (24/23472 African chromosomes) in the general population by the Genome Aggregation Database (gnomAD). The relatively high frequency of this variant in the general population suggests that this variant is unlikely to be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
CSER _CC_NCGL, University of Washington RCV000148682 SCV000190407 uncertain significance Primary familial hypertrophic cardiomyopathy 2014-06-01 no assertion criteria provided research
Clinical Genetics, Academic Medical Center RCV001698949 SCV001918661 uncertain significance not provided no assertion criteria provided clinical testing

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