Table 2.

Common RASopathy-associated mutations.

Component	Gene	Mutation	Domain	Type
Phosphatases	PPP1CB	p.P49R	N-terminus	NS
	PTPN11	p.D61G/N/H	N-SH2	NS
		p.Y63C
		p.Q79R/P
		p.N308D/S/T	Phosphatase
		p.Y279C/S		NS-ML
		p.T469M/P
RAS isoforms	HRAS	p.G12S/A/C	RAS	CS
	KRAS	p.V14I		NS
		p.P34R/K
		p.I36M
		p.T58I
		p.G60R/S
		p.D153V
	NRAS	p.G60E
	MRAS	p.G23R/V
	RRAS	p.G23dup
	RIT1	p.A57G
		p.F82l/I/V
		p.M90I
		G95A
Kinases	BRAF	p.Q257R/K	CRD	CFC
		p.L597V	Kinase
	RAF1	p.S257l/K/P	CR2	NS
	MEK1	p.Y130C/N/H	Kinase	CFC
	MEK2	p.F57C/I/V/l	N-terminus
GEFs	SOS1	p.M269T/R	RHO GEF	NS
		p.R552/G/S/K	Allosteric site
		p.E848K	RAS GEF
Ubiquitin	CBL	p.Y371H/C/N	RING	NSLD
	LZTR1	p.G248R	Kelch	NS

The table presents information about the most frequent recurring changes that occur in known RASopathy genes and specifies the protein domain where the alteration happens. The selection criteria were based on the clinical outcome (phenotype) of the variants. The acronyms used in the table include CFC, cardiofaciocutaneous syndrome; CS, Costello syndrome; NS, Noonan syndrome; NS-LAH, Noonan syndrome with loose anagen hair; NSLD, Noonan syndrome-like disease; NS-ML, Noonan syndrome with multiple lentigines.