Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000579923 | SCV000686218 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-27 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000708996 | SCV000838193 | uncertain significance | Lynch syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002529108 | SCV002992402 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-05-01 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 184 of the PMS2 protein (p.Met184Ile). This variant is not present in population databases (gnomAD no frequency). 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. 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. ClinVar contains an entry for this variant (Variation ID: 490108). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. |
Ambry Genetics | RCV000579923 | SCV004052675 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-10 | criteria provided, single submitter | clinical testing | The p.M184I variant (also known as c.552G>T), located in coding exon 6 of the PMS2 gene, results from a G to T substitution at nucleotide position 552. The methionine at codon 184 is replaced by isoleucine, an amino acid with highly similar 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. |