Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001010254 | SCV001170423 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-09-11 | criteria provided, single submitter | clinical testing | The p.G400E variant (also known as c.1199G>A), located in coding exon 10 of the CHEK2 gene, results from a G to A substitution at nucleotide position 1199. The glycine at codon 400 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001862763 | SCV002316940 | uncertain significance | Familial cancer of breast | 2021-03-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC 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. 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 818556). This sequence change replaces glycine with glutamic acid at codon 400 of the CHEK2 protein (p.Gly400Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. |