Table 2.

Likely pathogenic and pathogenic variants in both Tier 1 and Tier 2 genes

Case	Gene	Nucleotide variant	Amino acid variant	ACMG classification*	gnomAD MAF^	Varsome ACMG criteria†
Tier 1
090	ALDH18A1	NM_002860.4:c.1367G>A	p.Arg456His	Likely pathogenic	0.00004600	PM1, PM2, PP2, PP3
146	COL3A1	NM_000090.3:c.2798dupG	p.Ser934IlefsTer35	Pathogenic	-	PVS1, PM2, PP3
171	COL4A1	NM_001845.6:c.3592G>A	p.Gly1198Arg	Likely pathogenic	-	PM1, PM2, PP2, PP3
170	COL4A1	NM_001845.6:c.4877C>G	p.Ala1626Gly	Likely pathogenic	0.00000707	PM1, PM2, PP2, PP3
115	FBN1	NM_000138.4:c.793A>T	p.Thr265Ser	Likely pathogenic	-	PM1, PM2, PP2, PP3
004	FBN1	NM_000138.4:c.256C>T	p. Arg86Trp	Likely pathogenic	0.00001195	PM1, PM2, PP2, PP3
Tier 2
090	ACVR1	NM_001111067.4:c.1298A>G	p.Asp433Gly	Likely pathogenic	0.00000398	PM1, PM2, PP2, PP3
091	ACVR1	NM_001111067.4:c.1265G>A	p.Gly422Asp	Likely pathogenic	-	PM1, PM2, PP2, PP3

ACMG, American College of Medical Genetics; MAF, minor allele frequency.

^*ACMG classifications are automatically derived from Varsome and manually evaluated

^{^}gnomAD MAF refers to all populations.

^†ACMG interpretation criteria, detailed in Supplementary Table XV