ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.740C>G (p.Pro247Arg)

gnomAD frequency: 0.00001  dbSNP: rs1173245928
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001176941 SCV001341043 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001875830 SCV002244965 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-02-20 criteria provided, single submitter clinical testing 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. This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 247 of the PMS2 protein (p.Pro247Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 919017). 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 RCV001176941 SCV002671250 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-05 criteria provided, single submitter clinical testing The p.P247R variant (also known as c.740C>G), located in coding exon 7 of the PMS2 gene, results from a C to G substitution at nucleotide position 740. The proline at codon 247 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003987794 SCV004804120 uncertain significance not specified 2024-01-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004998680 SCV005625931 uncertain significance not provided 2024-07-17 criteria provided, single submitter clinical testing The PMS2 c.740C>G (p.Pro247Arg) variant has not been reported in individuals with PMS2-related conditions in the published literature. The frequency of this variant in the general population, 0.0000067 (1/149988 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas RCV003333761 SCV004041792 uncertain significance Lynch syndrome 4 2023-10-09 no assertion criteria provided clinical testing

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