ClinVar Miner

Submissions for variant NM_004281.3(BAG3):c.616A>C (p.Ile206Leu) (rs199700646)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226073 SCV000288307 uncertain significance Myofibrillar myopathy, BAG3-related; Dilated cardiomyopathy 1HH 2018-10-10 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 206 of the BAG3 protein (p.Ile206Leu). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is present in population databases (rs199700646, ExAC 0.009%). This variant has not been reported in the literature in individuals with BAG3-related disease. ClinVar contains an entry for this variant (Variation ID: 239790). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000443578 SCV000520095 uncertain significance not provided 2018-12-11 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the BAG3 gene. The I206L variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. In silico analysis suggests that this variant is probably damaging to the protein structure/function. However, the I206L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
Ambry Genetics RCV000617486 SCV000735872 uncertain significance Cardiovascular phenotype 2017-05-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Fulgent Genetics,Fulgent Genetics RCV000226073 SCV000894523 uncertain significance Myofibrillar myopathy, BAG3-related; Dilated cardiomyopathy 1HH 2018-10-31 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852427 SCV000995111 uncertain significance Cardiomyopathy; Premature ventricular contraction 2019-01-10 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000443578 SCV000924759 uncertain significance not provided 2016-09-13 no assertion criteria provided provider interpretation

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.