Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
University of Washington Department of Laboratory Medicine, |
RCV000210114 | SCV000266221 | uncertain significance | Lynch syndrome | 2015-11-20 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000567504 | SCV000670809 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-18 | criteria provided, single submitter | clinical testing | The p.C297S variant (also known as c.890G>C), located in coding exon 8 of the PMS2 gene, results from a G to C substitution at nucleotide position 890. The cysteine at codon 297 is replaced by serine, an amino acid with dissimilar properties. This variant was detected in an unaffected individual with a family history of ovarian cancer who underwent multigene panel testing and called a variant of uncertain significance by authors (Shirts BH et al. Genet Med, 2016 10;18:974-81). 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 | RCV000629731 | SCV000750687 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 297 of the PMS2 protein (p.Cys297Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 224586). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMS2 protein function. 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. |
Color Diagnostics, |
RCV000567504 | SCV000909668 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-26 | criteria provided, single submitter | clinical testing |