Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000524431 | SCV000552059 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-10-21 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with asparagine at codon 46 of the PMS2 protein (p.Ser46Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs121434629, ExAC 0.003%). This variant has been observed in individuals affected with clinical features of Lynch syndrome (PMID: 26866578, 25006859, Invitae). Also, this variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with constitutional mismatch repair deficiency syndrome (PMID: 18273873). ClinVar contains an entry for this variant (Variation ID: 91301). This variant has been reported to affect PMS2 protein function (PMID: 24027009). This variant disrupts the p.Ser46 amino acid residue in PMS2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22577899, 23709753). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Department of Pathology and Laboratory Medicine, |
RCV000076806 | SCV000592922 | likely pathogenic | Lynch syndrome | 2014-12-11 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000584471 | SCV000888391 | likely pathogenic | not provided | 2018-07-12 | criteria provided, single submitter | clinical testing | |
Color | RCV001185073 | SCV001351217 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-10-24 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Genetic Testing Laboratories, |
RCV000584471 | SCV000691980 | pathogenic | not provided | no assertion criteria provided | clinical testing |