Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000562844 | SCV000665318 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-23 | criteria provided, single submitter | clinical testing | The p.L280R variant (also known as c.839T>G), located in coding exon 6 of the CHEK2 gene, results from a T to G substitution at nucleotide position 839. The leucine at codon 280 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported with a carrier frequency of 0.00014 in 7051 unselected breast cancer patients and 0.00000 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083).This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001374211 | SCV001571002 | uncertain significance | Familial cancer of breast | 2024-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 280 of the CHEK2 protein (p.Leu280Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 481136). 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. 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. |
| Baylor Genetics | RCV001374211 | SCV004217522 | uncertain significance | Familial cancer of breast | 2023-10-05 | criteria provided, single submitter | clinical testing | |
| Center for Genomic Medicine, |
RCV003493652 | SCV004243022 | uncertain significance | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing |