Table 1.

Variant description of all NXK6‐2 mutations reported to date

Zygosity	cDNA change	Amino acid change	Type of mutation	Novel/known	ACMG score	ACMG classification	Onset	Phenotype	Additional signs reported	Hypomyelination	Cerebellar atrophy	Reference
Compound heterozygous	c.301C>A	p.Arg101Ser	Missense	Novel	PM2, PM3, PP1, PP3	Likely pathogenic	Childhood	Predominantly motor delay	Seizures	Mild	Yes	This study
	c.541C>G	p.Leu181Val	Missense	Known (rs369901030) (MAF = 0.0001170)	PM1, PM3, PP1, PP3	Likely pathogenic						This study
Compound heterozygous	c.571C>T	p.Gln191*	Nonsense	Novel	PVS1, PM1, PM2, PM3, PP1	Pathogenic	Neonatal	Severe global psychomotor delay	No	Diffuse, severe	No	This study
	c.592A>G	p.Asn198Asp	Missense	Novel	PM1, PM2, PM3, PP1	Likely pathogenic						This study
Homozygous	c.598C>T	p.Arg200Trp	Missense	Novel	PS1, PM1, PM2, PM3, PP1	Pathogenic	Neonatal	Severe global psychomotor delay	No	Diffuse, severe	Yes	This study
Homozygous	c.121A>T	p.Lys41*	Nonsense	Known	PVS1, PS3, PM2, PM3, PP1	Pathogenic	Childhood	Predominantly motor delay	Dystonia. Limitation of eye movements	Diffuse, severe	Yes	This study, Chelban et al. 2
Homozygous	c.196delC	p.Arg66Glyfs*122	Frameshift	Known	PVS1, PM2, PM3, PP1	Pathogenic	Neonatal	Severe global psychomotor delay	Limitation of eye movements, hearing impairment. Gastrostomy for severe dysphagia. Scoliosis	Diffuse, severe	No	This study, Anazi et al. 4, Baldi et al. 5
Homozygous	c.487C>G	p.Leu163Val	Missense	Known	PM1, PM2, PM3, PP1	Likely pathogenic	Neonatal	Severe global psychomotor delay	Seizures. Gastrostomy for severe dysphagia	Variable. 2 cases reported with no hypomyelination	Yes	This study, Chelban et al. 2, Baldi et al. 5
Homozygous	c.565G>T	p.Glu189*	Nonsense	Known	PVS1, PM1, PM2, PM3, PP1	Pathogenic	Neonatal	Severe global psychomotor delay	Severe dystonia	Diffuse, severe	Yes	Dorboz et al. 3
Compound heterozygous	c.589C>T	p.Gln197*	Nonsense	Known	PVS1, PM1, PM2, PM3, PP1	Pathogenic	Neonatal	Severe global psychomotor delay	Swallowing difficulties. Poor visual acuity	Diffuse, severe	No	Dorboz et al. 3
	c.599G>A	p.Arg200Gln	Missense	Known	PM1, PM2, PM3, PP1	Likely pathogenic
Homozygous	c.606delinsTA	p.Lys202Asnfs?1	Frameshift	Known	PVS1, PM1, PM2, PM3, PP1	Pathogenic	Neonatal	Severe global psychomotor delay	Severe dystonia	Diffuse, severe	Yes	Dorboz et al. 3
Homozygous	c.608G>A	p.Trp203*	Nonsense	Known	PVS1, PM1, PM2, PM3, PP1	Pathogenic	Neonatal	Severe global psychomotor delay	Seizures	Diffuse, severe	No	Baldi et al. 5

ACMG, The American College of Medical Genetics and Genomics.