ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.4450A>G (p.Ile1484Val)

dbSNP: rs772734618
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000759298 SCV000289380 uncertain significance not provided 2023-12-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1484 of the POLE protein (p.Ile1484Val). This variant is present in population databases (rs772734618, gnomAD 0.002%). 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: 240516). 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 with a negative predictive value of 80%. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759298 SCV000888541 uncertain significance not provided 2018-01-12 criteria provided, single submitter clinical testing
GeneDx RCV000759298 SCV001801565 uncertain significance not provided 2023-02-21 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
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003321568 SCV004027312 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing
GenomeConnect - Invitae Patient Insights Network RCV003483590 SCV004228640 not provided Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 07-27-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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