Submissions for variant NM_004281.4(BAG3):c.1296A>G (p.Val432=)

gnomAD frequency: 0.75935  dbSNP: rs196295

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037886	SCV000061548	benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Val432Val in Exon 04 of BAG3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence and has been identified in 24.3% (909/3738) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs196295).
Eurofins Ntd Llc (ga)	RCV000037886	SCV000112805	benign	not specified	2013-03-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000037886	SCV000167160	benign	not specified	2014-01-08	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.
PreventionGenetics, part of Exact Sciences	RCV000037886	SCV000310049	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000243961	SCV000317601	benign	Cardiovascular phenotype	2015-03-11	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	RCV000399004	SCV000360597	benign	Dilated cardiomyopathy 1HH	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.
Illumina Laboratory Services, Illumina	RCV000576644	SCV000360598	benign	Myofibrillar myopathy 6	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.
Athena Diagnostics	RCV000576644	SCV000677139	benign	Myofibrillar myopathy 6	2017-06-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590573	SCV000698276	benign	not provided	2017-08-04	criteria provided, single submitter	clinical testing	Variant summary: The BAG3 c.1296A>G (p.Val432Val) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESEfinder predicts that it affects binding of multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 89871/121300 control chromosomes (33720 homozygotes) from ExAC at a frequency of 0.7408986, which is approximately 18967 times the estimated maximal expected allele frequency of a pathogenic BAG3 variant (0.0000391), thus this variant is a very common benign polymorphism and allele G the wildtype allele at this position. In addition, multiple clinical diagnostic laboratories have classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals in literature. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001509888	SCV001716794	benign	Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000576644	SCV001774994	benign	Myofibrillar myopathy 6	2021-07-14	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000590573	SCV005320891	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000037886	SCV001742883	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037886	SCV001925673	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000037886	SCV001927626	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000037886	SCV001951033	benign	not specified		no assertion criteria provided	clinical testing