Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000799658 | SCV000939332 | uncertain significance | Familial cancer of breast | 2023-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 346 of the CHEK2 protein (p.Arg346Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of CHEK2-related conditions (PMID: 29470806). ClinVar contains an entry for this variant (Variation ID: 645557). 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. |
| Ambry Genetics | RCV002388468 | SCV002701413 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-28 | criteria provided, single submitter | clinical testing | The p.R346S variant (also known as c.1036C>A), located in coding exon 9 of the CHEK2 gene, results from a C to A substitution at nucleotide position 1036. The arginine at codon 346 is replaced by serine, an amino acid with dissimilar properties. This variant was observed in a study of 1010 unrelated Indian patients with breast and/or ovarian cancer (Singh J et al. Breast Cancer Res. Treat., 2018 Jul;170:189-196). This amino acid position is highly 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. |