Table 1.

Overview of the potentially disease-causing de novo variants identified in the targeted screen of all ANK3 PPI network members.

Gene	gDNA change (GRCh37 (hg19))	cDNA change	Protein change	Variant Type	CADD_Phred score	Domain	Neurodevelopmental phenotype
CSNK2A1	NC_000020.10:g.472926T>C	NM_177559.2:c.593A>G	p.(Lys198Arg)	missense	30	Activation loop (Lys198 responsible for recognition)	Developmental delay, hypotonia
CSNK2A1	NC_000020.10:g.476394T>C	NM_177559.2:c.479A>G	p.(His160Arg)	missense	24.7	Active site	Epilepsy, developmental delay, autism spectrum disorder
KCNQ2	NC_000020.10:g.62073826A>C	NM_172107.2:c.749T>G	p.(Val250Gly)	missense	25	Transmembrane helix 5	Epileptic encephalopathy, intellectual disability
KCNQ2	NC_000020.10:g.62044879C>T	NM_172107.2:c.1687G>A	p.(Asp563Asn)	missense	26.7	C-terminal cytoplasmic domain	Severe frontal epilepsy, autism spectrum disorder, severe intellectual disability, behavioural problems
SCN1A	NC_000002.11:g.166898844G>A	NM_001165963.1:c.2134C>T	p.(Arg712*)	nonsense	38	Cytoplasmic domain	Unexplained psychomotor problems
SCN1A	NC_000002.11:g.166852623C>T	NM_001165963.1:c.4481G>A	p.(Gly1494Glu)	missense	29.3	Cytoplasmic domain	Epilepsy (Dravet Syndrome), intellectual disability
SCN1B	NC_000019.9:g.35524482G>A	NM_001037.4:c.287G>A	p.(Arg96Gln)	missense	26.3	Extracellular domain	Developmental delay, mild intellectual disability, sleeping problems, severe psychiatric disorder (psychoses), craniosynostosis with scaphocephaly
SCN2A	NC_000002.11:g.166231477G>A	NM_001040142.1:c.4254 + 1G>A	p.?	splice site	23.3	—	Psychomotor retardation, epilepsy
SCN2A	NC_000002.11:g.166166923C>T	NM_021007.2:c.788 C>T	p.(Ala263Val)	missense	29.0	Transmembrane helix 5 repeat I	Intellectual disability, motor retardation, epilepsy/epileptiform EEG
SCN2A	NC_000002.11:g.166172167C>T	NM_021007.2:c.1570C>T	p.(Arg524*)	nonsense	29.7	Ankyrin-binding domain	Severe psychomotor retardation, autism spectrum disorder
SCN2A	NC_000002.11:g.166223837G>A	NM_021007.2:c.3631G>A	p.(Glu1211Lys)	missense	34.0	Transmembrane helix 1 repeat III	Unexplained psychomotor problems, infantile epileptic encephalopathy
SCN8A	NC_000012.11:g.52159701C>T	NM_014191.3:c.2791C>T	p.(Arg931*)	nonsense	42	Extracellular domain	Unexplained psychomotor problems, childhood absence epilepsy, behavioural problems, MRI abnormalities
SCN8A	NC_000012.11:g.52162973A>T	NM_014191.3:c.3226A>T	p.(Lys1076*)	nonsense	43	Ankyrin-binding domain	Developmental delay, intellectual disability, epilepsy
SCN8A	NC_000012.11:g.52162699C>G	NM_014191.3:c.2952C>G	p.(Asn984Lys)	missense	26.5	Cytoplasmic domain	Psychomotor retardation, therapy-resistent epilepsy