ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1042G>C (p.Glu348Gln)

dbSNP: rs1783538909
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001211487 SCV001383028 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 348 of the PMS2 protein (p.Glu348Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. 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 disruptive. 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 RCV002402625 SCV002708252 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-03 criteria provided, single submitter clinical testing The p.E348Q variant (also known as c.1042G>C), located in coding exon 10 of the PMS2 gene, results from a G to C substitution at nucleotide position 1042. The glutamic acid at codon 348 is replaced by glutamine, an amino acid with highly similar properties. In one study, this variant was detected in 0/165 colorectal cancer and/or polyposis patients and was identified in 1/2512 control individuals from a healthy population database (Rosenthal EA et al. Hum Genet, 2018 Oct;137:795-806). 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.
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV002402625 SCV004014926 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-09 criteria provided, single submitter clinical testing

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