Table 2. The heterozygous RUNX2 variants identified in the CCD patients.

Patient	Inheritance	Variants	Clinvar accession number	Zygosity	Variant type	Exon	Domain/Region	ACMG-AMP guideline	Status
1-I:2	Familial	c.739delA (p.(Ser247Valfs*3))	SCV001763563	Het	Frameshift	6	PST	Pathogenic	Novel
2-II:1 & 2-I:2	Familial	c.901C>T (p.(Gln301*))	SCV001763562	Het	Nonsense	7	PST	Pathogenic	Novel
3-II:1	NA	c.1081C>T (p.(Gln361*))	SCV001763561	Het	Nonsense	8	PST	Pathogenic	Novel
4-II:2	Sporadic	c.673C>T (p.(Arg225Trp))	SCV001780129	Het	Missense	5	RHD	Pathogenic	Previously reported†
5-II:1	Sporadic	c.674G>A (p.(Arg225Gln))	SCV002102512	Het	Missense	5	RHD	Pathogenic	Previously reported‡

M, male; F, female; NA, not available; RHD, Runt homologous domain; PST, proline-serine-threonine region; Del, deleterious; Het, heterozygous

ACMG-AMP, The American College of Medical Genetics and Genomics and the Association for Molecular Pathology

†1-10; ‡2, 5, 6, 8, 11-20 (References are provided in the supplementary figure 1 ^{(146.3KB, pdf)} )