ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.401G>A (p.Arg134Gln) (rs771300829)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482875 SCV000572919 uncertain significance not provided 2017-02-03 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.401G>A at the cDNA level, p.Arg134Gln (R134Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Arg134Gln 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 Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. PMS2 Arg134Gln occurs at a position where amino acids with properties similar to Arginine are tolerated across species and is located in the ATPase domain (Guarne 2001). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether PMS2 Arg134Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000630071 SCV000751027 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-09-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 134 of the PMS2 protein (p.Arg134Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs771300829, ExAC 0.02%). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 423246). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV001192083 SCV001360037 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-07 criteria provided, single submitter clinical testing

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