ClinVar Miner

Submissions for variant NM_004281.3(BAG3):c.512C>T (p.Ser171Phe) (rs794728978)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183316 SCV000235746 uncertain significance not provided 2018-04-10 criteria provided, single submitter clinical testing p.Ser171Phe (TCC>TTC): c.512 C>T in exon 3 of the BAG3 gene (NM_004281.3). Mutations in BAG3 account for approximately 2.5% of familial DCM cases (Hershberger RE and Morales A, 2013). Mutations in BAG3 may also cause myofibrillar myopathy type 6, which is characterized by early-onset, severe, progressive, diffuse muscle weakness associated with cardiomyopathy, severe respiratory insufficiency and spine rigidity (Hershberger RE and Morales A, 2013). The S171F variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The S171F 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. The S171F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. No missense mutations in nearby residues have been reported in association with DCM or myopathy, suggesting this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).

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