Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000167254 | SCV000218094 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-07 | criteria provided, single submitter | clinical testing | The p.E149G variant (also known as c.446A>G), located in coding exon 3 of the CHEK2 gene, results from an A to G substitution at nucleotide position 446. The glutamic acid at codon 149 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000700163 | SCV000828908 | uncertain significance | Familial cancer of breast | 2023-04-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 187519). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 149 of the CHEK2 protein (p.Glu149Gly). |
Gene |
RCV001753573 | SCV002006658 | uncertain significance | not provided | 2019-12-11 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek 2016); Has not been previously published as pathogenic or benign to our knowledge; Also known as c.575A>G, p.E192G |