ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.4476C>G (p.His1492Gln)

dbSNP: rs5744943
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000709256 SCV000838687 uncertain significance Familial colorectal cancer 2018-07-02 criteria provided, single submitter clinical testing
Invitae RCV003768091 SCV001531419 uncertain significance not provided 2023-07-16 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1492 of the POLE protein (p.His1492Gln). 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: 584834). 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).

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