Table 1.

Phenotypic data and Genetic findings: Reported patients with variants in TYR(NM_000372.5), MITF(NM_000248.4) and OCA2(NM_000275.3).

Proband (sex)	Age (yrs)	FH Grading	BCVA RE	BCVA LE	Allele 1	GnomAD v2.1.1 (MAF General Population)	ACMG Classification	Allele 2	Reference
P1 (F)	14	1	0.22	0.3	TYR: c.1037-7 T > A;p.?	0.0008614	Pathogenic (PS3,PP3,PP5, PM2)	TYR: c.1205G > A;p.R402Q TYR: c.575C > A;p.S192Y	(Spritz et al.,1993)
P2 (M)	8	2	0	0	TYR: c.1205G > A;p.R402Q TYR: c.455C > G;p.P152R	n.a	Likely Pathogenic (PM1,PM2,PM5)	TYR: c.1205G > A;p.R402Q TYR: c.575C > A;p.S192Y	(Rocca et al., 2022)
P3 (M)	11	1	0.22	0.1	OCA2: c.2245-6C > A;p.?	0.0001018	VUS (PM2,PP5,BP4)	OCA2:c.1256G > A;p.R419Q MC1R: c.451C > T;p.R151C	(Mauri et al., 2017)
P4 (M)	11	2	0.3	0.22	TYR: c.1205G > A;p.R402Q TYR: c.739 T > C;p.C247R	n.a	Pathogenic (PM1,PM2,PP3, PP5)	TYR: c.1205G > A;p.R402Q TYR: c.575C > A;p.S192Y	(Urtatiz, Sanabria, and Lattig, 2014)
P5 (F)	9	1	0	0	MITF: c.808C > T;p.R270*	n.a	Pathogenic (PVS1,PP5,PM2)	Wild type	(Sun et al., 2016)
P6 (F) P7 (F)	18 16	2 2	0.3 0.22	0.22 0.22	TYR: c.140G > A;p.G47D	0.0001556	Pathogenic (PM1,PM2, PM5,PP5)	TYR: c.1205G > A;p.R402Q TYR: c.575C > A;p.S192Y	(Marti et al.,2018;Oetting et al., 1993)
P8 (F)	14	1	0.4	0.1	TYR: c.575C > A;p.S192Y OCA2:c.1076G > A;p.G359D	0.000007964	Pathogenic (PM1,PM2, PM5,PP3,PP5)	TYR: c.575C > A;p.S192Y OCA2:c.1065G > A;p.A355 =	(Mauri et al., 2017)

Frequency data refer to the GnomAD v2.1.1 General Population. Polymorphisms are shown in bold: TYR: c.1205G > A (MAF: 0.1765), TYR: c.575C > A (MAF: 0.2502), OCA2:c.1256G > A (MAF: 0.04658), MC1R: c.451C > T (MAF: 0.04481), OCA2:c.1065G > A (MAF: 0.6353). The table shows frequency data and the ACMG classification for the rare variants. The results of segregation are discussed in the text. In P3 and P8 molecular results were inconclusive.