ClinVar Miner

Submissions for variant NM_004281.3(BAG3):c.679C>G (p.Gln227Glu) (rs149517238)

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Total submissions: 3
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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 Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (benign)
GeneDx 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.

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