ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5043C>G (p.Asn1681Lys)

dbSNP: rs1593729754
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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 RCV003772791 SCV002183219 uncertain significance not provided 2021-02-15 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 1681 of the POLE protein (p.Asn1681Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with POLE-related conditions. 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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 RCV003772791 SCV005375955 uncertain significance not provided 2023-11-29 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
Ambry Genetics RCV004945785 SCV005478964 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-08 criteria provided, single submitter clinical testing The p.N1681K variant (also known as c.5043C>G), located in coding exon 38 of the POLE gene, results from a C to G substitution at nucleotide position 5043. The asparagine at codon 1681 is replaced by lysine, 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. Based on the available evidence, the clinical significance of this variant remains unclear.

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