ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.2083T>C (p.Phe695Leu)

dbSNP: rs5744799
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000759270 SCV000289283 uncertain significance not provided 2025-01-28 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 695 of the POLE protein (p.Phe695Leu). This variant is present in population databases (rs5744799, gnomAD 0.008%). This missense change has been observed in individual(s) with personal or family history of POLE-related conditions (PMID: 35534704). ClinVar contains an entry for this variant (Variation ID: 240419). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 RCV000759270 SCV000888504 uncertain significance not provided 2017-10-26 criteria provided, single submitter clinical testing
GeneDx RCV000759270 SCV001757820 uncertain significance not provided 2025-01-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in an individual with a family history of colorectal and other cancers undergoing multigene hereditary cancer panel testing (PMID: 35534704); This variant is associated with the following publications: (PMID: 20951805, 29056344, 29458332, 35534704)
Mendelics RCV003993904 SCV002519181 likely benign Hereditary cancer-predisposing syndrome 2024-04-09 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV004596140 SCV005089977 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005008192 SCV005633745 uncertain significance Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome; Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency 2024-02-08 criteria provided, single submitter clinical testing

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