Submissions for variant NM_004281.4(BAG3):c.249C>A (p.His83Gln)

gnomAD frequency: 0.00344  dbSNP: rs151331972

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000037891	SCV000051367	benign	not specified	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037891	SCV000061553	benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.His83Gln in Exon 02 of BAG3: This variant is not expected to have clinical sig nificance because it has been identified in 1.0% (39/3738) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs151331972).
GeneDx	RCV000513197	SCV000167153	benign	not provided	2018-11-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25617006, 30086531)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082899	SCV000561198	benign	Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000513197	SCV000608570	uncertain significance	not provided	2017-03-01	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852640	SCV000995345	benign	Primary dilated cardiomyopathy	2018-02-07	criteria provided, single submitter	clinical testing
Mendelics	RCV000988453	SCV001138174	benign	Myofibrillar myopathy 6	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000513197	SCV001157652	benign	not provided	2020-08-11	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000037891	SCV001433227	benign	not specified	2019-07-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037891	SCV001442729	benign	not specified	2020-10-01	criteria provided, single submitter	clinical testing	Variant summary: BAG3 c.249C>A (p.His83Gln) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.001 in 282862 control chromosomes, predominantly at a frequency of 0.01 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 256 fold of the estimated maximal expected allele frequency for a pathogenic variant in BAG3 causing Dilated Cardiomyopathy phenotype (3.9e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (1x) and benign (5x). Based on the evidence outlined above, the variant was classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149635	SCV003837859	benign	Cardiomyopathy	2022-03-23	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037891	SCV001917283	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000037891	SCV001965055	benign	not specified		no assertion criteria provided	clinical testing