Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000544695 | SCV000633191 | uncertain significance | Familial cancer of breast | 2021-10-24 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Ile157 amino acid residue in CHEK2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11298456, 11571648, 12049740, 15239132, 15492928, 22419737, 22799331, 23296741, 23713947, 24599715). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is present in population databases (rs748262921, ExAC 0.006%). This sequence change replaces isoleucine with valine at codon 157 of the CHEK2 protein (p.Ile157Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. |