ClinVar Miner

Submissions for variant NM_004281.3(BAG3):c.1067del (p.Pro356fs) (rs727505109)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000156562 SCV000206281 likely pathogenic Primary dilated cardiomyopathy 2016-04-15 criteria provided, single submitter clinical testing The p.Pro356fs variant in BAG3 has been identified by our laboratory in 1 Caucas ian individual with DCM. It was absent from large population studies. This varia nt is predicted to cause a frameshift, which alters the protein?s amino acid seq uence beginning at position 356 and leads to a premature termination codon 7 ami no acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of functions variants in BAG3 have been reported to be dis ease-causing (Norton 2011, Villard, 2011). In summary, although additional studi es are required to fully establish its clinical significance, the p.Pro356fs var iant is likely pathogenic.
Invitae RCV000476824 SCV000550844 likely pathogenic Dilated cardiomyopathy 1HH 2016-06-02 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 4 of the BAG3 mRNA (c.1067delC), causing a frameshift at codon 356. This creates a premature translational stop signal in the last exon of the BAG3 mRNA (p.Pro356Hisfs*7). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated BAG3 protein. This variant is not present in population databases (rs727505109, ExAC no frequency) and has not been reported in the literature in individuals with a BAG3-related disease. ClinVar contains an entry for this variant (Variation ID: 179764). A different truncation downstream of this position (p.Leu423Lysfs*14) is reported to be deleterious (PMID: 24623017). This indicates that the truncation affects residues that are important for BAG3 protein function. In the absence of additional functional and/or genetic data, this variant has been classified as Likely Pathogenic.

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