Table 2. Classification of mutations.

Varianta	Mutationa	Severity groupc	SIFTd	Exon	Type, location	Functional effecte	Allele frequencies
p.G591D	c.1772G>A	Moderate	0.42	5	Missense, Cu 6	Extensive mislocalization	1% (1/70)
p.R616Q	c.1847G>A	Moderate	0.07	5	Missense		1% (1/70
Ex5-6delb	c.1708-?_1946+?del	Severe	—	5–6	Deletion, Cu 6		1% (1/70)
p.D642H	c.1924G>C	Moderate	0.05	6	Missense, Cu6/TM1		3% (2/70)
p.I669I-fs	c.2007_2013delATATGCT	Moderate	—	7	Deletion, TM1		6% (4/70)
p.M769H-fs	c.2304insC	Severe	—	8	Insertion, TM4		1% (1/70)
p.M769V	c.2305A>G	Moderate	0.52	8	Missense, TM4	Normal rescue ΔCcc2 yeast. Normal cellular localization	3% (2/70)
p.R778 L	c.2333G>T	Severe	0.01	8	Missense, TM4	Reduced rescue ΔCcc2 yeast. Extensive mislocalization	3% (2/70)
p.W779X	c.2336G>A	Severe	0.00	8	Non-sense, TM4		12% (8/70)
p.G943D	c.2828G>A	Severe	0.02	12	Missense, TM5		4% (3/70)
p.T977M	c.2930C>T	Severe	0.00	13	Missense, TM6	No rescue ΔCcc2 yeast	1% (1/70)
p.A1003T	c.3007G>A	Moderate	0.00	13	Missense, TM6		1% (1/70)
p.I1021 Kb	c.3062T>A	Severe	0.00	14	Missense, ATP		3% (2/70)
p.R1041W	c.3121C>T	Moderate	0.03	14	Missense, ATP loop, N-domain		3% (2/70)
p.H1069Q	c.3207C>A	Severe	0.00	14	Missense, ATP loop, N-domain	No/reduced rescue ΔCcc2 yeast. Extensive mislocalization	18% (12/70)
p.G1158Vb	c.3473G>T	Moderate	0.03	16	Missense, ATP loop, N-domain		1% (1/70)
p.M1169T	c.3506T>C	Moderate	0.01	16	Missense, ATP loop, N-domain		3% (2/70)
p.T1220M	c.3659C>T	Severe	0.00	17	Missense, ATP binding P-domain		6% (4/70)
p.G1266R	c.3796G>A	Severe	0.00	18	Missense, ATP hinge, P-domain		6% (4/70)
p.N1270S	c.3620A>G	Severe	0.00	18	Missense, ATP hinge, P-domain	Reduced ATP hydrolysis activity	3% (2/70)
p.P1273 L	c.3818C>T	Severe	0.00	18	Missense, ATP hinge, P-domain		3% (3/70)
p.L1304Fb	c.3912G>T	Severe	0.00	19	Missense, between ATP hinge and TM7		3% (2/70)
p.G1341D	c.4022G>A	Severe	0.02	20	Missense, TM7		1% (1/70)
p.Q1351X	c.4051C>T	Moderate	0.00	20	Non-sense, loop between TM7-TM8		1% (1/70)
p.S1363F	c.4088C>T	Severe	0.00	20	Missense, TM 8		6% (4/70)
IVS20-2A>Gb	c.4022-2A>G	Moderate	—	Intron 20	Splice-site, skipping of exon 21		1% (1/70)
Ex20-21del	c.4022-?_4398+?del	Severe	—	20-21	TM8, C-ter		3% (2/70)

^aNucleotide numbering refers to the cDNA numbering, where +1 is the A of the ATG translation initiation codon in the reference sequence. Codon 1 is the initiation codon, ATG.

^bNew mutations in bold letters, reported for the first time in this study.

^cSevere, age of onset<20 years; moderate, age of onset>20 years.

^dSIFT: predicts whether a substitution can be tolerated or not: >0.05 tolerated; <0.05 affect protein function.

^eReviewed in de Bie et al.³⁶