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These variants can represent low\u2010penetrance LFS, mosaic LFS, or clonal hematopoiesis of indeterminate potential. Additionally, <jats:italic>TP53<\/jats:italic> variants of uncertain significance can be detected in patients with a history suspicious for LFS. The interpretation of the significance of these variants can be challenging but is crucial for an accurate diagnosis and appropriate medical management. This retrospective case review provides illustrative examples of the interpretation of challenging <jats:italic>TP53<\/jats:italic> results through multidisciplinary expertise and use of a flowchart. The authors describe eight patients with <jats:italic>TP53<\/jats:italic> variants associated with ambiguous diagnoses and, for each case, describe how the results were interpreted and the medical care that was implemented. This report presents illustrative cases to help guide clinicians to reach definitive diagnoses for patients when confronted with <jats:italic>TP53<\/jats:italic> variants that are inconsistent with the clinical picture and to add to the body of literature regarding interpretation and medical management of <jats:italic>TP53<\/jats:italic> variants discovered on germline testing.<\/jats:p>","DOI":"10.1002\/jgc4.1789","type":"journal-article","created":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T17:04:07Z","timestamp":1694883847000},"page":"916-926","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Interpretation of ambiguous <scp><i>TP53<\/i><\/scp> test results: Mosaicism, clonal hematopoiesis, and variants of uncertain significance"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2585-3926","authenticated-orcid":false,"given":"Darcy K.","family":"Berry","sequence":"first","affiliation":[{"name":"Department of Individualized Cancer Management H. 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