ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.502G>A (p.Val168Met)

gnomAD frequency: 0.00001  dbSNP: rs762645507
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165453 SCV000216183 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-06 criteria provided, single submitter clinical testing The p.V168M variant (also known as c.502G>A), located in coding exon 5 of the PMS2 gene, results from a G to A substitution at nucleotide position 502. The valine at codon 168 is replaced by methionine, 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 inconclusive by in silico analyses. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000481889 SCV000569478 uncertain significance not provided 2023-08-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27820796, 11574484)
Color Diagnostics, LLC DBA Color Health RCV000165453 SCV000686213 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000822639 SCV000963449 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-12-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 168 of the PMS2 protein (p.Val168Met). This variant is present in population databases (rs762645507, gnomAD 0.0009%). 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: 185940). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt PMS2 function with a negative predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV002492659 SCV002777946 uncertain significance Lynch syndrome 4; Mismatch repair cancer syndrome 4 2021-11-09 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000481889 SCV004026208 uncertain significance not provided 2022-11-15 criteria provided, single submitter clinical testing PP3, PM2_SUP
Baylor Genetics RCV004567274 SCV005056429 uncertain significance Lynch syndrome 4 2024-02-13 criteria provided, single submitter clinical testing

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