Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000548810 | SCV000633240 | uncertain significance | Familial cancer of breast | 2023-07-22 | 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: 460867). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is present in population databases (rs774685647, gnomAD 0.003%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 329 of the CHEK2 protein (p.Tyr329Cys). |
| Ambry Genetics | RCV002384085 | SCV002695783 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-31 | criteria provided, single submitter | clinical testing | The p.Y329C variant (also known as c.986A>G), located in coding exon 8 of the CHEK2 gene, results from an A to G substitution at nucleotide position 986. The tyrosine at codon 329 is replaced by cysteine, an amino acid with highly dissimilar properties. 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. |