ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.802G>A (p.Asp268Asn)

dbSNP: rs2043060847
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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 RCV001772306 SCV001236391 uncertain significance not provided 2022-07-01 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 268 of the POLE protein (p.Asp268Asn). This variant has not been reported in the literature in individuals affected with POLE-related conditions. 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. 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 C0"). ClinVar contains an entry for this variant (Variation ID: 864014).
GeneDx RCV001772306 SCV002002958 uncertain significance not provided 2020-02-07 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 RCV002411619 SCV002675531 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-01 criteria provided, single submitter clinical testing The p.D268N variant (also known as c.802G>A) is located in coding exon 9 of the POLE gene. The aspartic acid at codon 268 is replaced by asparagine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 9. 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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