Table 4.

Clinical features of the individuals with variants in CAMK2D

	1	2	3	4	5	6	7	8	Total
Variant nomenclature chr4 (GRCh37)a
Genome	g.114530307C>A	g.114530347C>T	g.114458598G>A	g.114438787C>T	g.114435068T>G	g.114435065C>T	g.114435065C>T	g.114435016C>G	7 variants 1 SS, 6 MS
Nucleotides	c.275+1G>T	c.236G>A	c.416C>T	c.628G>A	c.821A>C	c.824G>A	c.824G>A	c.873G>C
Amino acids	p.?	p.Ser79Asn	p.Pro139Leu	p.Gly210Arg	p.Gln274Pro	p.Arg275His	p.Arg275His	p.Leu291Phe
Variant annotation
MobiDetailsb	92725	93616	93619	272319	93654	93656	93656	93659
CADD (v.1.6)	34	25.90	33	26.30	24.90	24.60	24.60	22.50
Metadome (tolerance score)	N/A	neutral	highly intolerant	unknown	intolerant	intolerant	intolerant	highly intolerant
MPA	10 (high splice)	6 (moderate missense)	7 (moderate missense)	7 (moderate missense)	5 (low missense)	5 (low missense)	5 (low missense)	5 (low missense)
Revel	N/A	uncertain	damaging	damaging	uncertain	uncertain	uncertain	uncertain
ClinPred	N/A	damaging	damaging	damaging	damaging	damaging	damaging	damaging
Mistic	N/A	damaging	damaging	damaging	damaging	damaging	damaging	damaging
gnomAD v.2.1.1	absent	absent	absent	absent	absent	absent	absent	absent
ClinVar	SCV002103284	SCV002103285	SCV002103286	SCV003799177	SCV002103287	SCV002103288	SCV002103288	SCV002103289
Mode of inheritance	de novo	de novo	de novo	de novo	de novo	dominant	dominant	de novo
Method of mutation detection	ES	ES	ES	ES	ES	ES	ES	GS
Gender	female	female	male	male	female	male	female	male	4 F, 3 M
Age at last investigation	11 years	2 years	4 years	6 years	20 years	12 years	17 years	5 weeks	5 weeks to 19 years
Height at age last investigation (SD)	+1.69	−1.14	−2.86	−1.37	−3.28	−0.94	−2.1	−1.14	−3.28 to −0.94
Developmental delay or ID	+; mild	+; moderate to severe	+; severe	+; severe	+; profound	+; mild	+; severe	ND	7/7
Delay in walking	+	+	+	+	+	+	+	ND	7/7
Speech delay	+	+; non-verbal	+; non-verbal	+; vocalizations only	+; non-verbal	+; mixed receptive-expressive language disorder	+; non-verbal	ND	7/7
Dysmorphic facial features	+	+	+	+	+	+	+	–	7/8
Skeletal anomalies	+; hands, feet	+; spine	+; thorax	+; hands, feet, thorax, palate	+; feet, thorax	+; hands	+; hands, feet, palate	–	7/8
Dilated cardiomyopathy	–	+; cardiac transplantation	+; planned cardiac transplantation	–	+; severe, cardiac transplantation impossible; VSD repaired, PDA	+; cardiac transplantation	+; severe; AtSD and PAPVR repaired	+; severe	6/8
Abnormal muscle tone	+	+	+	+	+	–	–	–	5/8
Seizures	+	–	–	–	+	–	–	–	2/8
Behavioral anomalies	+; ASD	+; ASD	+	+	+; ASD	+; ADHD	+; ASD	ND	7/7
Digestive problems	–	+; GJ tube feeding	+; NJ feeding	+; chronic constipation	+; tube feeding, EoE, dysphagia, megacolon	ND	ND	–	4/6
Visual anomalies	+	+	ND	+	+	ND	+	ND	5/5
Urogenital/kidney anomalies	–	–	+	–	+	ND	ND	–	2/6
Anomalies in brain imaging	+; enlarged ventricles	+; enlarged ventricles	+; hemorrhagic infarcts	+; enlarged ventricles	+; decreased brain volume	ND	ND	ND	5/5
EEG anomalies	+	–	ND	+	ND	ND	ND	ND	2/3

N/A, not applicable; ND, not determined; SD, standard deviation; ES, exome sequencing; GS, genome sequencing; VSD, ventricular; AtSD, atrial septal defect septal defect; PDA, patent ductus arteriosus; ASD, autism spectrum disorder; ADHD, attention deficit/hyperactivity disorder; GJ tube feeding, gastrostomy-jejunostomy tube feeding; NJ feeding, naso-jejunal feeding; EoE, eosinophilic esophagitis; PAPVR, partial anomalous pulmonary venous return.

^aNomenclature HGVS v.2.0 according to mRNA reference sequence GenBank: NC_000004.11 (NM_001321579.2) for the splice site variant in individual 1 and GenBank: NM_001321579.2 for missense variants in individuals 2–9. Nucleotide numbering uses +1 as the A of the ATG translation initiation codon in the reference sequence, with the initiation codon as codon 1.

^bFor online access, insert the accession number in place of <XXX> at https://mobidetails.iurc.montp.inserm.fr/MD/api/variant/<XXX>/browser/