TABLE 1.

Clinical features of each proband outlined by major systems involved

	Clinical features
Subject	Vertebral malformations	Cardiac	CNS	KIAA1217 variant (transcript NM_019590, build 37/hg19)	HVAR	CADD	gnomAD Frequency
Proband 1	C+, T ± Fusion	ASD		Exon3: c.G433A:p.Ala145Thr	0	–	1.789e-4
Proband 2	C Fusion		Hydrocephalus Macrocephaly	Exon19: c.A4219T:p.Lys1407X	0.73	8.03	0
Proband 3	C Fusion	Dextrocardia and VSD	Tethered cord	Exon6: c.C1039T:p.Pro347Ser	0.81	4.91	8.127e-6
Proband 4	C Fusion			Exon13: c:G2503T:pAla835Ser	0.997	14.39	0
	T VM¶			Exon13: c:C2660T:pAla887Val	0.013	0.01	4.587e-4
Proband 5	C, T Fusion		Tethered cord	Exon19: c.5039 T > C:p.Ile1680Tyr	0.964	15.64	2.032e-5
Proband 6	C Fusion	Myocarditis		Exon17: c.5800G > T:p.Ala1934Ser	0.01	5.177	1.931e-4
	T VM
Proband 7	C Fusion T VM			Exon14: c.3131C > T:p.Ser1044Leu	0.67	28.7	2.924e-5
Proband 8	C Fusion T, L§ VM			Exon19: c.3877A > G:p.Ile1293Val	0	0	1.234e-4
Proband 9	C Fusion			Exon7: c.901G > A:p.Gly301Arg	12.9	12.9	2.853e-5
Proband 10	C Fusion incomplete segmentation	Small ASD VSD	Cerebellar tonsillar prolapse into spinal canal Basilar invagination Sprengel deformity	Exon2: c.A185G:p.Asn62Ser	0.337	18.12	3.934e-4

Note: +Cervical, ± Thoracic

^§Lumbar, and

^¶Vertebral; Probands 1–3, 10 USA; Probands 4–9 Peking Union Medical College Hospital.

Details of each variant identified and their gnomAD frequency. Proband 2 also has an Xq21.1 deletion, which contains exons 1–29 of the BRWD3 gene. LOF variants in BRWD3 are associated with X-linked non-syndromic intellectual disability and macrocephaly. However, this does not explain the vertebral phenotype observed in this individual. +Cervical, ± Thoracic, § Lumbar, and ¶ Vertebral malformation.