Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000527677 | SCV000625514 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 416 of the PMS2 protein (p.Ser416Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of PMS2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 455646). 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. |
| Ambry Genetics | RCV002395284 | SCV002674421 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | The p.S416C variant (also known as c.1247C>G), located in coding exon 11 of the PMS2 gene, results from a C to G substitution at nucleotide position 1247. The serine at codon 416 is replaced by cysteine, an amino acid with dissimilar properties. 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. |
| Gene |
RCV003441914 | SCV004168496 | uncertain significance | not provided | 2023-10-11 | 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; Identified in an individual with a personal history of a Lynch-related tumor and/or polyps who also harbored a pathogenic BRCA2 variant (Yurgelun et al., 2015); This variant is associated with the following publications: (PMID: 25980754) |
| Baylor Genetics | RCV003470717 | SCV004205450 | uncertain significance | Lynch syndrome 4 | 2023-09-12 | criteria provided, single submitter | clinical testing |