Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000244314 | SCV000320475 | uncertain significance | Cardiovascular phenotype | 2015-11-20 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (benign) |
Gene |
RCV000426389 | SCV000529860 | uncertain significance | not provided | 2018-07-17 | criteria provided, single submitter | clinical testing | The Q227E variant in the BAG3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Q227E variant is observed in 9/126578 (0.007%) alleles from individuals of non-Finnish European background, in large population cohorts (Lek et al., 2016). The Q227E variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret Q227E as a variant of uncertain significance. |
Invitae | RCV000685071 | SCV000812543 | uncertain significance | Myofibrillar myopathy, BAG3-related; Dilated cardiomyopathy 1HH | 2018-05-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 227 of the BAG3 protein (p.Gln227Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs149517238, ExAC 0.005%). This variant has not been reported in the literature in individuals with BAG3-related disease. ClinVar contains an entry for this variant (Variation ID: 264497). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; 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. |