Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000569238 | SCV000666361 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-06-04 | criteria provided, single submitter | clinical testing | The p.G525E variant (also known as c.1574G>A), located in coding exon 14 of the CHEK2 gene, results from a G to A substitution at nucleotide position 1574. The glycine at codon 525 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is not 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 | RCV002530252 | SCV003472621 | uncertain significance | Familial cancer of breast | 2023-03-07 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 525 of the CHEK2 protein (p.Gly525Glu). ClinVar contains an entry for this variant (Variation ID: 481715). 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. |