Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000214614 | SCV000275101 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-21 | criteria provided, single submitter | clinical testing | The p.M381L variant (also known as c.1141A>C), located in coding exon 10 of the CHEK2 gene, results from an A to C substitution at nucleotide position 1141. The methionine at codon 381 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly 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 | RCV000554690 | SCV000633100 | uncertain significance | Familial cancer of breast | 2022-09-23 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 231297). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is present in population databases (rs375130261, gnomAD 0.0009%). This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 381 of the CHEK2 protein (p.Met381Leu). |
Gene |
RCV001594878 | SCV001829536 | uncertain significance | not provided | 2019-12-16 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Baylor Genetics | RCV001833223 | SCV002096968 | uncertain significance | Li-Fraumeni syndrome 2 | 2022-01-07 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |