ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1481G>A (p.Arg494Gln)

gnomAD frequency: 0.00001  dbSNP: rs192173820
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001284686 SCV001394206 uncertain significance not provided 2024-12-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 494 of the POLE protein (p.Arg494Gln). This variant is present in population databases (rs192173820, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 950418). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt POLE protein function with a positive 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284686 SCV001470614 uncertain significance not provided 2019-12-27 criteria provided, single submitter clinical testing
GeneDx RCV001284686 SCV004021656 uncertain significance not provided 2023-07-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32647357)

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