SGK1 mutations confer aberrant splicing and translation of hyperstable protein isoforms. The most common mutations occur in hotspot regions at the start of exon 2, which leads to the generation of 2 aberrantly spliced messenger RNA (mRNA ) neoisoforms. In addition, the mutations lead to disruption of the reading frame introducing premature stop codons. This provokes initiation of translation from downstream methionines, resulting in an N-terminally truncated hyperstable protein with preserved kinase domain but with lack of degradation domain. Created with BioRender.com.