Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000131787 | SCV000186836 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-05-17 | criteria provided, single submitter | clinical testing | The p.L338R variant (also known as c.1013T>G), located in coding exon 9 of the CHEK2 gene, results from a T to G substitution at nucleotide position 1013. The leucine at codon 338 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV000131787 | SCV000292203 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000287814 | SCV000329281 | uncertain significance | not provided | 2018-05-24 | criteria provided, single submitter | clinical testing | This variant is denoted CHEK2 c.1013T>G at the cDNA level, p.Leu338Arg (L338R) at the protein level, and results in the change of a Leucine to an Arginine (CTT>CGT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. CHEK2 Leu338Arg was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the protein kinase domain (Cai 2009, Roeb 2012). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether CHEK2 Leu338Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Invitae | RCV001222751 | SCV001394867 | uncertain significance | Familial cancer of breast | 2023-08-25 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 142584). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is present in population databases (rs374660293, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 338 of the CHEK2 protein (p.Leu338Arg). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002307405 | SCV002600327 | uncertain significance | not specified | 2022-10-06 | criteria provided, single submitter | clinical testing |