ClinVar Miner

Submissions for variant NM_004281.3(BAG3):c.855_859dup (p.Leu287fs) (rs1057518511)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413342 SCV000492236 likely pathogenic not provided 2016-12-02 criteria provided, single submitter clinical testing A novel c.855_859dupGCCAC variant that is likely pathogenic was identified in the BAG3 gene. The c.855_859dupGCCAC variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant causes a shift in reading frame starting at codon Leucine 287, changing it to an Arginine, and creating a premature stop codon at position 22 of the new reading frame, denoted p.Leu287ArgfsX22. This likely pathogenic variant is expected to result in a prematurely truncated protein product at the last exon of BAG3 without nonsense-mediated decay. Other frameshift variants in the BAG3 gene have been reported in HGMD in association with DCM, and most are downstream of this variant (Stenson et al., 2014). Nonetheless, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined.Therefore, this variant is likely pathogenic. In order to definitively determine its clinical significance, additional data is required.
Invitae RCV001040522 SCV001204101 pathogenic Myofibrillar myopathy, BAG3-related; Dilated cardiomyopathy 1HH 2019-03-18 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the BAG3 gene (p.Leu287Argfs*22). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 289 amino acids of the BAG3 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BAG3-related conditions. ClinVar contains an entry for this variant (Variation ID: 373624). This variant disrupts the C-terminus of the BAG3 protein. Other variant(s) that disrupt this region (p.Arg309*) have been determined to be pathogenic (PMID: 25448463). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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.