RNF43 and Leigh syndrome: For example the PTCC from 2008 had a FGFR3R248C pathogenic variant that is enriched in upper urothelial tract cancers arising in LS patients17; the CRC from 2015 had variants of unknown significance (VUS) in PIK3CAH510N and SMAD4G230V whereas the CRC from 2018 had somatic indels in TGFBR2 and RNF43, all of which are frequent somatic targets in CRCs6, while the TNBC from 2017 had a frame shift indel in PTEN and a FANCMS789X nonsense variant in each of the three sorted biopsies.