Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000708736 | SCV000822139 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001059903 | SCV001224557 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 312 of the PMS2 protein (p.Met312Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 31159747). ClinVar contains an entry for this variant (Variation ID: 584547). 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 not expected to disrupt PMS2 protein function with a negative predictive value of 80%. 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 | RCV000708736 | SCV002682317 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-01 | criteria provided, single submitter | clinical testing | The p.M312L variant (also known as c.934A>T), located in coding exon 9 of the PMS2 gene, results from an A to T substitution at nucleotide position 934. The methionine at codon 312 is replaced by leucine, an amino acid with highly similar properties. This variant was detected in 1/1197 individuals with a personal or family history of breast and/or ovarian cancer from a Greek, Romanian, and Turkish cohort (Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |