Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000635827 | SCV000757252 | uncertain significance | Familial cancer of breast | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 491 of the CHEK2 protein (p.Met491Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 530145). 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 tolerated. 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 | RCV002388040 | SCV002697517 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-13 | criteria provided, single submitter | clinical testing | The p.M491L variant (also known as c.1471A>T), located in coding exon 13 of the CHEK2 gene, results from an A to T substitution at nucleotide position 1471. The methionine at codon 491 is replaced by leucine, an amino acid with highly similar properties. In one study, this variant was identified in 1/1058 participants with colorectal cancer (Yurgelun MB et al. J. Clin. Oncol., 2017 Apr;35:1086-1095). 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. |