ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1700A>G (p.Gln567Arg) (rs112104877)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481815 SCV000572040 uncertain significance not provided 2016-10-17 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.1700A>G at the cDNA level, p.Gln567Arg (Q567R) at the protein level, and results in the change of a Glutamine to an Arginine (CAG>CGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Gln567Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. PMS2 Gln567Arg occurs at a position that is not conserved and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether PMS2 Gln567Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000694864 SCV000823326 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-06-14 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 567 of the PMS2 protein (p.Gln567Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 422543). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Mendelics RCV000987823 SCV001137288 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2019-05-28 criteria provided, single submitter clinical testing

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