ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.516A>T (p.Glu172Asp)

dbSNP: rs1785191843
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001245060 SCV001418322 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-07-15 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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. 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. ClinVar contains an entry for this variant (Variation ID: 969665). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 172 of the PMS2 protein (p.Glu172Asp).
Ambry Genetics RCV002339680 SCV002641378 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-18 criteria provided, single submitter clinical testing The p.E172D variant (also known as c.516A>T), located in coding exon 5 of the PMS2 gene, results from an A to T substitution at nucleotide position 516. The glutamic acid at codon 172 is replaced by aspartic acid, an amino acid with highly similar 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478752 SCV004219012 uncertain significance not provided 2023-06-06 criteria provided, single submitter clinical testing This variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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