ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1936A>G (p.Arg646Gly)

dbSNP: rs369582237
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001052616 SCV001216836 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-04-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 646 of the PMS2 protein (p.Arg646Gly). 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: 848785). 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 RCV002409438 SCV002723813 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-19 criteria provided, single submitter clinical testing The p.R646G variant (also known as c.1936A>G), located in coding exon 11 of the PMS2 gene, results from an A to G substitution at nucleotide position 1936. The arginine at codon 646 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004570194 SCV005056491 uncertain significance Lynch syndrome 4 2023-12-04 criteria provided, single submitter clinical testing

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