ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.3245G>T (p.Arg1082Leu)

dbSNP: rs201744227
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003656878 SCV001531459 uncertain significance not provided 2022-08-25 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1035032). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1082 of the POLE protein (p.Arg1082Leu).
New York Genome Center RCV001337843 SCV002506818 uncertain significance Colorectal cancer, susceptibility to, 12 2021-05-28 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002268472 SCV002550124 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002322269 SCV002609803 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-24 criteria provided, single submitter clinical testing The p.R1082L variant (also known as c.3245G>T), located in coding exon 26 of the POLE gene, results from a G to T substitution at nucleotide position 3245. The arginine at codon 1082 is replaced by leucine, an amino acid with dissimilar 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 RCV003656878 SCV005370879 uncertain significance not provided 2023-07-23 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

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