Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569750 | SCV000673248 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-21 | criteria provided, single submitter | clinical testing | The p.F201S variant (also known as c.602T>C), located in coding exon 4 of the CHEK2 gene, results from a T to C substitution at nucleotide position 602. The phenylalanine at codon 201 is replaced by serine, an amino acid with highly dissimilar properties. This alteration was identified in 1/1207 cases of French women diagnosed with breast cancer who had a sister with breast cancer and were BRCA1 and BRCA2 negative and 0/1199 general population controls (Girard E et al. Int J Cancer, 2019 04;144:1962-1974). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003117339 | SCV003787187 | uncertain significance | Familial cancer of breast | 2022-07-20 | 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 485516). This missense change has been observed in individual(s) with breast cancer (PMID: 30303537). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 201 of the CHEK2 protein (p.Phe201Ser). |
| Baylor Genetics | RCV003117339 | SCV004217618 | uncertain significance | Familial cancer of breast | 2023-07-27 | criteria provided, single submitter | clinical testing |