ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.2683G>A (p.Ala895Thr) (rs201115064)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657053 SCV000322161 uncertain significance not provided 2018-12-11 criteria provided, single submitter clinical testing This variant is denoted POLE c.2683G>A at the cDNA level, p.Ala895Thr (A895T) at the protein level, and results in the change of an Alanine to a Threonine (GCC>ACC). This variant was reported in at least two individuals with an attenuated polyposis phenotype, but no reported family history, and has been observed in a family with an autism spectrum disorder (Cukier 2014, Spier 2014). POLE Ala895Thr was observed at an allele frequency of 0.06% (15/25,788) in individuals of Finnish ancestry in large population cohorts (Lek 2016). POLE Ala895Thr is located in the polymerase domain (Preston 2010). In silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on currently available evidence, it is unclear whether POLE Ala895Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000472688 SCV000543990 likely benign Colorectal cancer, susceptibility to, 12 2019-12-26 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000255380 SCV000596499 uncertain significance not specified 2017-04-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000657053 SCV000602013 uncertain significance not provided 2019-01-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV000569257 SCV000671313 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-18 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient or conflicting evidence
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000255380 SCV000712561 uncertain significance not specified 2016-11-15 criteria provided, single submitter clinical testing The p.Ala895Thr variant in POLE has been reported in 2 individuals with colorect al adenomatous polyposis with an attenuated phenotype (Spier 2015). This variant has also been identified in 47/66724 of European chromosomes by the Exome Aggre gation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201115064). Com putational prediction tools and conservation analysis suggest that the p.Ala895T hr variant may impact the protein, though this information is not predictive eno ugh to determine pathogenicity. In summary, the clinical significance of the p.A la895Thr variant is uncertain.
Counsyl RCV000472688 SCV000785069 uncertain significance Colorectal cancer, susceptibility to, 12 2017-03-30 criteria provided, single submitter clinical testing
Mendelics RCV000709264 SCV000838695 uncertain significance COLORECTAL CANCER 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765065 SCV000896262 uncertain significance Colorectal cancer, susceptibility to, 12; Facial dysmorphism, immunodeficiency, livedo, and short stature 2018-10-31 criteria provided, single submitter clinical testing
Mendelics RCV000472688 SCV001138889 uncertain significance Colorectal cancer, susceptibility to, 12 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000657053 SCV001148895 uncertain significance not provided 2017-03-01 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000569257 SCV000788171 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-12 no assertion criteria provided clinical testing

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