ClinVar Miner

Submissions for variant NM_004281.3(BAG3):c.1385T>C (p.Leu462Pro) (rs397514507)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000437344 SCV000520850 likely pathogenic not provided 2017-01-31 criteria provided, single submitter clinical testing The L462P variant in the BAG3 gene was reported previously in one individual with DCM, and wasalso present in a sibling with regional hypokinesia of the posterior ventricular wall but not overt DCM(Arimura et al., 2011). Functional studies indicated this variant led to cytoplasmic BAG3 aggregation,abnormal Z-disc assembly, and sensitivity to apoptosis (Arimura et al., 2011). The L462P variant wasnot observed in approximately 6500 individuals of European and African American ancestry in theNHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.The L462P variant is a semi-conservative amino acid substitution, which may impact secondaryprotein structure as these residues differ in some properties. This substitution occurs at a position thatis conserved across species. In silico analysis predicts this variant is probably damaging to the proteinstructure/function. Therefore, L462P is a strong candidate for a pathogenic variant, however the possibility it maybe a rare benign variant cannot be excluded.
OMIM RCV000032661 SCV000056424 pathogenic Dilated cardiomyopathy 1HH 2011-12-01 no assertion criteria provided literature only

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