ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1325A>G (p.Glu442Gly)

dbSNP: rs1230334566
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002479261 SCV001204262 uncertain significance not provided 2022-11-22 criteria provided, single submitter clinical testing 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 POLE protein function. ClinVar contains an entry for this variant (Variation ID: 839009). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 442 of the POLE protein (p.Glu442Gly).
Sema4, Sema4 RCV002259068 SCV002536744 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-23 criteria provided, single submitter curation
Quest Diagnostics Nichols Institute San Juan Capistrano RCV002479261 SCV002774704 uncertain significance not provided 2021-07-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV002259068 SCV003854675 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-05 criteria provided, single submitter clinical testing The p.E442G variant (also known as c.1325A>G), located in coding exon 13 of the POLE gene, results from an A to G substitution at nucleotide position 1325. The glutamic acid at codon 442 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. 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.

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