ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.73G>A (p.Ala25Thr)

gnomAD frequency: 0.00001  dbSNP: rs773204331
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235639 SCV000293977 uncertain significance not provided 2016-02-16 criteria provided, single submitter clinical testing This variant is denoted POLE c.73G>A at the cDNA level, p.Ala25Thr (A25T) at the protein level, and results in the change of an Alanine to a Threonine (GCC>ACC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. POLE Ala25Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Alanine and Threonine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. POLE Ala25Thr occurs at a position that is not conserved and is not located in a known functional domain (Tahirov 2009, Preston 2010). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether POLE Ala25Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000235639 SCV000543972 uncertain significance not provided 2024-11-05 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 25 of the POLE protein (p.Ala25Thr). This variant is present in population databases (rs773204331, gnomAD 0.006%). 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: 246425). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV000235639 SCV001134762 uncertain significance not provided 2019-03-27 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.