Table 2.

Mutations identified in CPS1D patients (mutations reported before are shown in bold type)

Patient	Exon	Nucleotide change	Amino acid substitution	CPS1 domain	In silico investigation			Highest MAFd	Population frequencye
					PolyPhen‐2a	SIFTb	MutPred2c
P1	Exon5	c.478G > A	p.A160T	ISD	1	0.002	0.832	–	–
	Exon11	c.1145C > T f	p.P382L	GSD	0.865	0.015	0.518	<0.01	0
P2	Exon23	c.2865_c.2869delAAACT	p.T955Tfs*12	UFSD	–	–	–	–	–
	Exon33	c.3949C > T	p.R1317W	CPSD	0.998	0	0.882	–	–
P3	Exon1	c.1145C > T f	p.P382L	GSD	0.865	0.015	0.518	<0.01	0
	Exon17	c.1958T > G	p.V653G	BPSD	0.845	0.001	0.842	–	–
P4	Exon16	c.1760G > A g	p.R587H	BPSD	1	0	0.925	–	–
	Exon33	c.3945G > A	p.W1315X(186)	CPSD	–	–	–	–	–
P5	Exon11	c.1271A > T h	p.E379V	GSD	0.995	0	0.682	<0.01	1.163 e‐04
	Exon32	c.3928C > T h	p.P1265S	CPSD	1	0.001	0.735	<0.01	–

^aPolyPhen‐2 grades the damaging effect of an amino acid substitution as “probably damaging” if the score is between 0.909 and 1, and “possibly damaging” if the score is between 0.447 and 0.908, and “benign” is the score is between 0 and 0.446.

^bSIFT scores the substitution as ≤0.05 = damaging, which means that the change is predicted to affect protein function.

^cMutPred2 scores the probability that the amino acid substitution is pathogenic. A score threshold of 0.50 would suggest pathogenicity.

^dHighest minor allele frequency observed in any population including 1000 genomes phase 3, ESP, and gnomAD.

^eThe frequency of the East Asian population documented by the Exome Aggregation Consortium (ExAC).

^fRef.3

^gRef.3, 9, 15

^hThe mutation has been listed in the single nucleotide polymorphism databases (dbSNP) without a case report.