ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.6083G>C (p.Arg2028Thr)

gnomAD frequency: 0.00001  dbSNP: rs749132017
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003159147 SCV000772786 uncertain significance not provided 2024-08-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 2028 of the POLE protein (p.Arg2028Thr). This variant is present in population databases (rs749132017, gnomAD 0.002%). 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: 540819). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV002358880 SCV002656255 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-23 criteria provided, single submitter clinical testing The p.R2028T variant (also known as c.6083G>C), located in coding exon 44 of the POLE gene, results from a G to C substitution at nucleotide position 6083. The arginine at codon 2028 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003159147 SCV003852813 uncertain significance not provided 2022-10-03 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
CeGaT Center for Human Genetics Tuebingen RCV003159147 SCV005894125 uncertain significance not provided 2024-12-01 criteria provided, single submitter clinical testing POLE: PM2, BP4

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