Submissions for variant NM_004281.4(BAG3):c.1002T>G (p.Pro334=)

gnomAD frequency: 0.12375  dbSNP: rs3858339

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037883	SCV000061545	benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Pro334Pro 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 17.0% (637/3738) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs3858339).
Eurofins Ntd Llc (ga)	RCV000037883	SCV000112803	benign	not specified	2013-03-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000037883	SCV000167158	benign	not specified	2014-01-20	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	RCV000037883	SCV000310046	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000249466	SCV000317751	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	RCV000269109	SCV000360589	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	RCV000576828	SCV000360590	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	RCV000576828	SCV000677137	benign	Myofibrillar myopathy 6	2017-06-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590170	SCV000698273	benign	not provided	2017-08-03	criteria provided, single submitter	clinical testing	Variant summary: The BAG3 c.1002T>G (p.Pro334Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect biding of multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 13883/121360 control chromosomes (1030 homozygotes) from ExAC at a frequency of 0.1143952, which is approximately 2928 times the estimated maximal expected allele frequency of a pathogenic BAG3 variant (0.0000391), thus it is a common benign polymorphism. In addition, multiple clinical diagnostic laboratories have classified this variant as benign. In literature, this variant has been reported in one patient with dilated cardiomyopathy who also carried a rare variant p.I206V and known polymorphisms c.910-21A>C and p.P407L (Ruppert_2013). Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001514277	SCV001722078	benign	Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH	2025-02-04	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000590170	SCV005320889	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000037883	SCV001917506	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000037883	SCV001954222	benign	not specified		no assertion criteria provided	clinical testing