Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001012879 | SCV001173393 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-15 | criteria provided, single submitter | clinical testing | The p.L58F variant (also known as c.172C>T), located in coding exon 3 of the PMS2 gene, results from a C to T substitution at nucleotide position 172. The leucine at codon 58 is replaced by phenylalanine, 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. |
Invitae | RCV001304292 | SCV001493568 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-01-03 | 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: 819927). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 58 of the PMS2 protein (p.Leu58Phe). |
All of Us Research Program, |
RCV004004520 | SCV004814297 | uncertain significance | Lynch syndrome | 2023-03-04 | criteria provided, single submitter | clinical testing | |
Constitutional Genetics Lab, |
RCV001249989 | SCV001424003 | uncertain significance | Lynch-like syndrome | 2019-07-01 | no assertion criteria provided | clinical testing |