ClinVar Miner

Submissions for variant NM_004281.4(BAG3):c.367C>T (p.Arg123Ter) (rs387906875)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000211711 SCV000061554 likely pathogenic Primary dilated cardiomyopathy 2017-01-27 criteria provided, single submitter clinical testing The p.Arg123X variant in BAG3 has been identified in 4 adults with DCM and segre gated with disease in 5 affected relatives (Norton 2011, LMM data). This variant has also been identified in 2/66492 European chromosomes by the Exome Aggregati on Consortium (ExAC,; dbSNP rs387906875). This no nsense variant leads to a premature termination codon at position 123, which is predicted to lead to a truncated or absent protein. Loss of function variants in BAG3 are strongly associated with DCM. In summary, although additional studies are required to fully establish its clinical significance, the p.Arg123X variant is likely pathogenic.
Ambry Genetics RCV000247382 SCV000318449 pathogenic Cardiovascular phenotype 2019-01-21 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000254992 SCV000322083 pathogenic not provided 2017-04-11 criteria provided, single submitter clinical testing The R123X variant in the BAG3 gene has been reported in one family with dilated cardiomyopathy (Norton et al., 2011). The R123X variant was first identified in a proband with dilated cardiomyopathy and history of heart transplantation at 26 years of age. It was subsequently identified in two siblings, one with mild LV dysfunction and the other with asymptomatic dilated cardiomyopathy, and in their father with an unspecified type of cardiomyopathy and history of heart transplantation at 40 years of age. The R123X variant was absent in 2,644 control chromosomes (Norton et al., 2011). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R123X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R123X as a pathogenic variant
Invitae RCV000627789 SCV000550842 pathogenic Myofibrillar myopathy, BAG3-related; Dilated cardiomyopathy 1HH 2019-02-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 123 (p.Arg123*) of the BAG3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BAG3 are known to be pathogenic (PMID: 21353195, 25008357). This particular variant has been reported in the literature in a family affected with dilated cardiomyopathy (PMID: 21353195). ClinVar contains an entry for this variant (Variation ID: 30397). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000627789 SCV000893146 pathogenic Myofibrillar myopathy, BAG3-related; Dilated cardiomyopathy 1HH 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000023350 SCV000044641 pathogenic Dilated cardiomyopathy 1HH 2011-03-11 no assertion criteria provided literature only
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000254992 SCV000924755 likely pathogenic not provided 2018-01-29 no assertion criteria provided provider interpretation

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