ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1199A>G (p.Gln400Arg)

dbSNP: rs148069478
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000687650 SCV000815232 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 400 of the PMS2 protein (p.Gln400Arg). 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: 567536). 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.
Color Diagnostics, LLC DBA Color Health RCV000771538 SCV000904097 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000771538 SCV002643057 uncertain significance Hereditary cancer-predisposing syndrome 2020-11-06 criteria provided, single submitter clinical testing The p.Q400R variant (also known as c.1199A>G), located in coding exon 11 of the PMS2 gene, results from an A to G substitution at nucleotide position 1199. The glutamine at codon 400 is replaced by arginine, 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.

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