Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000233610 | SCV000289660 | uncertain significance | Familial cancer of breast | 2023-03-10 | 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: 240736). This variant is also known as c.1436T>G. This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 436 of the CHEK2 protein (p.Leu436Arg). |
| Ambry Genetics | RCV002379013 | SCV002693775 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-06-18 | criteria provided, single submitter | clinical testing | The p.L436R variant (also known as c.1307T>G), located in coding exon 11 of the CHEK2 gene, results from a T to G substitution at nucleotide position 1307. The leucine at codon 436 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 women with breast cancer and 0.0000 in 11241 female controls; and with a carrier frequency of 0.0000 in 53 unselected men with breast cancer and 0.0001 in 12490 male controls (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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477830 | SCV004221723 | uncertain significance | not provided | 2022-12-03 | criteria provided, single submitter | clinical testing | It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in a large breast cancer association study in individuals affected with breast cancer as well as in unaffected individuals (PMID: 30287823 (2018)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |