ClinVar Miner

Submissions for variant NM_004281.4(BAG3):c.463G>A (p.Ala155Thr) (rs61756328)

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Total submissions: 12
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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 RCV000037894 SCV000051365 benign not specified 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037894 SCV000061556 likely benign not specified 2017-01-23 criteria provided, single submitter clinical testing p.Ala155Thr in exon 2 of BAG3: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, wallaby, opossum, and platypus have a threonine (Thr) at this position despi te high nearby amino acid conservation. Computational analyses (AlignGVGD, PolyP hen2, SIFT) do not suggest a high likelihood of impact to the protein. In additi on, it has been identified in 0.5% (294/63478) of European (Non-Finnish) chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.orgdb SNP; rs61756328).
GeneDx RCV000037894 SCV000235736 benign not specified 2017-11-10 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 RCV001080256 SCV000261251 benign Myofibrillar myopathy, BAG3-related; Dilated cardiomyopathy 1HH 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000037894 SCV000310057 likely benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000247095 SCV000318572 benign Cardiovascular phenotype 2017-12-01 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification;General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000037894 SCV000333198 likely benign not specified 2015-07-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000315530 SCV000360564 uncertain significance Dilated cardiomyopathy 1HH 2018-01-12 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 Clinical Services Laboratory,Illumina RCV000353959 SCV000360565 benign Myofibrillar myopathy, BAG3-related 2018-01-12 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.
Integrated Genetics/Laboratory Corporation of America RCV000590411 SCV000698279 benign not provided 2017-08-16 criteria provided, single submitter clinical testing Variant summary: The BAG3 c.463G>A (p.Ala155Thr) variant involves the alteration of a non-conserved nucleotide. 4/5 in silico tools predict benign outcome for this variant. This variant was found in 352/117428 control chromosomes (4 homozygotes) from ExAC and literature at a frequency of 0.0029976, which is approximately 77 times the estimated maximal expected allele frequency of a pathogenic BAG3 variant (0.0000391), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases in ClinVar classified this variant as benign/likely benign. It is also regarded as benign in the literature (Ng_2013). To our knowledge, this variant t has not been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000037894 SCV000740454 likely benign not specified 2017-01-27 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852641 SCV000995346 benign Hypertrophic cardiomyopathy 2018-06-15 criteria provided, single submitter clinical testing

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