Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001034985 | SCV001198290 | uncertain significance | Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH | 2019-04-04 | criteria provided, single submitter | clinical testing | 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. 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: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with BAG3-related conditions. This variant is present in population databases (rs201487919, ExAC 0.006%). This sequence change replaces glycine with cysteine at codon 192 of the BAG3 protein (p.Gly192Cys). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and cysteine. |
| Fulgent Genetics, |
RCV001034985 | SCV002800748 | uncertain significance | Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH | 2021-10-06 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV003145255 | SCV003829749 | uncertain significance | not provided | 2022-04-11 | criteria provided, single submitter | clinical testing | |
| Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV003339430 | SCV004048261 | uncertain significance | Myofibrillar myopathy 6 | criteria provided, single submitter | clinical testing | The missense variant c.574G>T (p.Gly192Cys) in BAG3 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database as Uncertain Significance. The p.Gly192Cys variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.002002% is reported in gnomAD . The amino acid Gly at position 192 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Gly192Cys in BAG3 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance . |