ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5907A>C (p.Glu1969Asp)

dbSNP: rs1060504069
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000679655 SCV000806822 uncertain significance not provided 2017-06-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679655 SCV000889777 uncertain significance not provided 2017-09-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002352099 SCV002653261 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-20 criteria provided, single submitter clinical testing The p.E1969D variant (also known as c.5907A>C), located in coding exon 43 of the POLE gene, results from an A to C substitution at nucleotide position 5907. The glutamic acid at codon 1969 is replaced by aspartic acid, an amino acid with highly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000679655 SCV003344200 uncertain significance not provided 2024-06-20 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1969 of the POLE protein (p.Glu1969Asp). 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: 560847). 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.
GeneDx RCV000679655 SCV005331874 uncertain significance not provided 2024-01-16 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

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