ClinVar Miner

Submissions for variant NM_004281.4(BAG3):c.1417C>T (p.Arg473Ter)

dbSNP: rs199682693
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000760914 SCV000890810 likely pathogenic not provided 2018-12-24 criteria provided, single submitter clinical testing The R473X likely pathogenic variant in the BAG3 gene has been reported in a patient diagnosed with dilated cardiomyopathy in infancy (Janin et al., 2017). This variant is predicted to cause loss of normal protein function by protein truncation as the last 102 amino acids are deleted. Other nonsense variants in the BAG3 gene have been reported in Human Gene Mutation Database in association with cardiomyopoathy (Stenson et al., 2014). Furthermore, the R473X variant is not observed in large population cohorts (Lek et al., 2016). In summary, R473X in the BAG3 gene is interpreted as a likely pathogenic variant.
Invitae RCV001056928 SCV001221395 likely pathogenic Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH 2023-07-07 criteria provided, single submitter clinical testing This variant disrupts a region of the BAG3 protein in which other variant(s) (p.Arg477His) have been observed in individuals with BAG3-related conditions (PMID: 21353195). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 620529). This sequence change creates a premature translational stop signal (p.Arg473*) in the BAG3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 103 amino acid(s) of the BAG3 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with dilated cardiomyopathy (PMID: 28436997, 32160020).
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV001256782 SCV001433226 likely pathogenic Dilated cardiomyopathy 1A 2019-08-28 criteria provided, single submitter clinical testing

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