Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000809939 | SCV000950122 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 184 of the PMS2 protein (p.Met184Thr). This variant is not present in population databases (gnomAD no frequency). 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: 654051). 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 with a positive 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. |
Division of Medical Genetics, |
RCV001257485 | SCV001434295 | uncertain significance | Lynch syndrome 4 | 2019-12-16 | criteria provided, single submitter | clinical testing | To our knowledge, this sequence variant has not been previously reported in the literature. This variant is not present in population databases (https://gnomad.broadinstitute.org/). In silico analyses indicate this is an evolutionarily conserved residue. Thus, it is unknown at this time whether this variant increases cancer risk. PM2; PP3 |
Sema4, |
RCV002256534 | SCV002530361 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-23 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002256534 | SCV002648700 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-26 | criteria provided, single submitter | clinical testing | The p.M184T variant (also known as c.551T>C), located in coding exon 6 of the PMS2 gene, results from a T to C substitution at nucleotide position 551. The methionine at codon 184 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV003235405 | SCV003932942 | uncertain significance | not provided | 2022-12-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 11574484) |