ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.3713G>A (p.Ser1238Asn)

dbSNP: rs879255392
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000238742 SCV000297204 uncertain significance not specified 2015-11-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003539870 SCV000772689 uncertain significance not provided 2024-10-07 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1238 of the POLE protein (p.Ser1238Asn). 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: 252660). 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 RCV003165674 SCV003898910 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-09 criteria provided, single submitter clinical testing The p.S1238N variant (also known as c.3713G>A), located in coding exon 30 of the POLE gene, results from a G to A substitution at nucleotide position 3713. The serine at codon 1238 is replaced by asparagine, 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.
GeneDx RCV003539870 SCV005078212 uncertain significance not provided 2023-08-09 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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