ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.3209A>G (p.Lys1070Arg)

dbSNP: rs2042628757
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001772277 SCV001223090 uncertain significance not provided 2023-08-09 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POLE protein function. ClinVar contains an entry for this variant (Variation ID: 853658). 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 lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1070 of the POLE protein (p.Lys1070Arg).
GeneDx RCV001772277 SCV002001209 uncertain significance not provided 2020-11-25 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); 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 RCV002320309 SCV002609337 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-29 criteria provided, single submitter clinical testing The p.K1070R variant (also known as c.3209A>G), located in coding exon 26 of the POLE gene, results from an A to G substitution at nucleotide position 3209. The lysine at codon 1070 is replaced by arginine, 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.

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