Submissions for variant NM_004281.3(BAG3):c.1447G>A (p.Gly483Ser) (rs570294713)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000604718	SCV000728180	likely benign	not specified	2018-03-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000809395	SCV000949545	uncertain significance	Myofibrillar myopathy, BAG3-related; Dilated cardiomyopathy 1HH	2018-09-17	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with serine at codon 483 of the BAG3 protein (p.Gly483Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs570294713, ExAC 0.01%). This variant has not been reported in the literature in individuals with BAG3-related disease. ClinVar contains an entry for this variant (Variation ID: 515906). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.