Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000482023 | SCV000565379 | uncertain significance | not provided | 2016-09-26 | criteria provided, single submitter | clinical testing | This variant is denoted PMS2 c.19T>C at the cDNA level, p.Ser7Pro (S7P) at the protein level, and results in the change of a Serine to a Proline (TCG>CCG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Ser7Pro was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Serine and Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. PMS2 Ser7Pro occurs at a position that is not conserved and is located in the ATPase domain (Guarne 2001, Fukui 2011). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether PMS2 Ser7Pro is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Invitae | RCV001851139 | SCV002302746 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-01-30 | criteria provided, single submitter | clinical testing | 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 not expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 418412). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 7 of the PMS2 protein (p.Ser7Pro). |
Ambry Genetics | RCV003298542 | SCV004005580 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-30 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |