ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.6853G>T (p.Gly2285Cys)

dbSNP: rs1245794040
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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 RCV001772078 SCV000943913 uncertain significance not provided 2024-07-15 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 2285 of the POLE protein (p.Gly2285Cys). This variant is not present in population databases (gnomAD no frequency). 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: 649156). 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 disruptive. 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.
GeneDx RCV001772078 SCV001993780 uncertain significance not provided 2023-05-25 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; This variant is associated with the following publications: (PMID: 31034466, 29056344)
Ambry Genetics RCV002360966 SCV002665536 uncertain significance Hereditary cancer-predisposing syndrome 2024-08-02 criteria provided, single submitter clinical testing The p.G2285C variant (also known as c.6853G>T), located in coding exon 49 of the POLE gene, results from a G to T substitution at nucleotide position 6853. The glycine at codon 2285 is replaced by cysteine, an amino acid with highly 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.

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