Table 2.

Mutations detected in PD, NPD and LSCC cases by NGS.

	Mutated sample	Gene	Genomic position	Genetic modification	AA change	Functional Classificationa	COSMIC	dbSNP ID	MAF (ExAC)	Clinical variationb	References
Progressing dysplasia and associated LSCC	PD1+PD5	PIK3CA	chr3:178936082	c.1624G>A	p.E542K	Gain-of-function	COSM760	rs121913273	NR	Pa	28,29,49
	PD1+PD5	FGFR3	chr4:1803568	c.746C>G	p.S249C	Gain-of-function	COSM715	rs121913483	G=0.000010/1	Pa	28,30,31
	PD2, LSCC2	TP53	chr17:7577082	c.856G>A	p.E286K	Loss-of-function	COSM10726, COSM99924	NR	NA	NA	25,29
	PD4, LSCC4		chr17:7577085	c.853G>A	p.E285K	Loss-of-function	COSM10722; COSM137087	rs112431538	NA	NR	30,50
	PD4, LSCC4		chr17:7577099	c.839G>T	p.R280I	Loss-of-function	COSM11287	rs121912660	NA	Pa
	PD3, LSCC3		chr17:7578212	c.637C>T	p.R213*	Loss-of-function	COSM10654; COSM99615, COSM99616, COSM99617, COSM99618	rs397516436	A=0.000008/1	Pa	25,26,29
Non-progressing dysplasia	NPD3		chr17:7578403	c.527G>T	p.C176F	Partial gain	COSM10645	NR	NA	NA	51
	NPD3	JAK3	chr19:17945696	c.2164G>A	p.V722I	Gain-of-function	COSM34213	rs3213409	T=0.0086/1048	UA
	NPD5	MET	chr7:116411923	c.2962C>T	p.R988C	Gain-of-function	NOCOSMIC988	rs34589476	T=0.0029/343	US
	NPD6	FBXW7	chr4:153247289	c.1273C>A	p.R425C	uncertain	NR	NR	NR	NR

^aThe effect of the mutation on protein function was determined from published studies, and for TP53 mutations on the overall transcriptional activity on eight different promoters as measured in yeast assays by Kato et al.²¹.

^bClinical significance on ClinVar submissions (as recommended by the American College of Medical Genetics and Genomics). MAF, minor allele frequency (1000 genomes project); PD, progressing dysplasia; LSCC, laryngeal squamous cell carcinoma; NPD, non-progressing dysplasia; chr, chromosome; NA, not applicable; NR, not reported; Pa, pathogenic; UA, untested allele; US, uncertain significance.