Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000222705 | SCV000277568 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-02 | criteria provided, single submitter | clinical testing | The p.R294Q variant (also known as c.881G>A), located in coding exon 8 of the PMS2 gene, results from a G to A substitution at nucleotide position 881. The arginine at codon 294 is replaced by glutamine, an amino acid with highly similar 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. |
Invitae | RCV000473195 | SCV000551977 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 294 of the PMS2 protein (p.Arg294Gln). This variant is present in population databases (rs373239341, gnomAD 0.007%). This missense change has been observed in individual(s) with breast cancer (PMID: 34326862). ClinVar contains an entry for this variant (Variation ID: 233232). 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 with a negative predictive value of 80%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
Gene |
RCV000486648 | SCV000569365 | uncertain significance | not provided | 2020-12-16 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as a pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 27093186) |
Counsyl | RCV000662988 | SCV000785977 | uncertain significance | Lynch syndrome 4 | 2018-01-29 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000708991 | SCV000838187 | uncertain significance | Lynch syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000222705 | SCV000903867 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-04 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 294 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/251388 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Mendelics | RCV000662988 | SCV001137312 | uncertain significance | Lynch syndrome 4 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000486648 | SCV002047138 | uncertain significance | not provided | 2021-05-18 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000662988 | SCV004019830 | uncertain significance | Lynch syndrome 4 | 2023-04-04 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Baylor Genetics | RCV000662988 | SCV004205459 | uncertain significance | Lynch syndrome 4 | 2023-09-05 | criteria provided, single submitter | clinical testing |