ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.3968C>T (p.Ala1323Val)

gnomAD frequency: 0.00007  dbSNP: rs550525366
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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 RCV001284212 SCV000821678 uncertain significance not provided 2025-01-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1323 of the POLE protein (p.Ala1323Val). This variant is present in population databases (rs550525366, gnomAD 0.02%). 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: 572422). 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 RCV001284212 SCV001469873 uncertain significance not provided 2020-03-19 criteria provided, single submitter clinical testing
Baylor Genetics RCV001825353 SCV002096976 uncertain significance Facial dysmorphism-immunodeficiency-livedo-short stature syndrome 2022-01-11 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001284212 SCV002571424 uncertain significance not provided 2024-04-30 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV005010694 SCV005633714 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 2024-04-23 criteria provided, single submitter clinical testing

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