ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1573G>A (p.Gly525Arg)

dbSNP: rs1265449448
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000688266 SCV000815871 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 525 of the PMS2 protein (p.Gly525Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 568030). 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%. 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 RCV003163120 SCV003853889 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-27 criteria provided, single submitter clinical testing The p.G525R variant (also known as c.1573G>A), located in coding exon 11 of the PMS2 gene, results from a G to A substitution at nucleotide position 1573. The glycine at codon 525 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. 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.

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