Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000461608 | SCV000550450 | uncertain significance | Familial cancer of breast | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with phenylalanine at codon 211 of the CHEK2 protein (p.Val211Phe). The valine residue is moderately conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. 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"). 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. |
Ambry Genetics | RCV002356686 | SCV002655228 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-26 | criteria provided, single submitter | clinical testing | The p.V211F variant (also known as c.631G>T), located in coding exon 4 of the CHEK2 gene, results from a G to T substitution at nucleotide position 631. The valine at codon 211 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |