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Although PZM is a common biological phenomenon, it is often overlooked as a source of disease due to the challenges associated with its detection and characterization, especially for very low\u2010frequency variants. Moreover, PZM can cause a different phenotype compared to constitutional mutations. Especially, lethal mutations in receptor tyrosine kinase (RTK) pathway genes, which exist only in a mosaic state, can have completely new clinical manifestations and can look very different from the associated monogenic disorder. However, some key questions are still not addressed, such as the level of mosaicism resulting in a pathogenic phenotype and how the clinical outcome changes with the development and age. Addressing these questions is not trivial as we require methods with the sensitivity to capture some of these variants hidden away in very few cells. Recent ultra\u2010accurate deep\u2010sequencing approaches can now identify these low\u2010level mosaics and will be central to understand systemic and local effects of mosaicism in the RTK pathway. The main focus of this review is to highlight the importance of low\u2010level mosaics and the need to include their detection in studies of genomic variation associated with disease.<\/jats:p>","DOI":"10.1111\/febs.15528","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T01:44:45Z","timestamp":1598579085000},"page":"3108-3119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pathogenic postzygotic mosaicism in the tyrosine receptor kinase pathway: potential unidentified human disease hidden away in a few cells"],"prefix":"10.1111","volume":"288","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3621-7020","authenticated-orcid":false,"given":"Irene","family":"Tiemann\u2010Boege","sequence":"first","affiliation":[{"name":"Institute of Biophysics Johannes Kepler University Linz 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