Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000213815 | SCV000275430 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-24 | criteria provided, single submitter | clinical testing | The p.E8D variant (also known as c.24G>T), located in coding exon 1 of the CHEK2 gene, results from a G to T substitution at nucleotide position 24. The glutamic acid at codon 8 is replaced by aspartic acid, an amino acid with highly 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 | RCV000635939 | SCV000757366 | uncertain significance | Familial cancer of breast | 2023-07-07 | criteria provided, single submitter | clinical testing | 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 aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 231544). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is present in population databases (rs780920036, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 8 of the CHEK2 protein (p.Glu8Asp). |
Gene |
RCV003238741 | SCV003936454 | uncertain significance | not provided | 2023-06-29 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |