Table 3.

All identified pathogenic variants in PRPH2, CRX, PROM1, and CERKL genes in study cases^*

Patient ID	Clinical Pheno-type	Gene	Transcript	cDNA	Protein	Zygosity	gnomAD MAF†	CADD‡	Mode	Segre-gation	Reported	Pathogenic Criteriaa
3239	STGD1	PRPH2	ENST00000230381	c.584G>A	p.Arg195Gln	het	-	32.0	AD		+ °	PM2, PM5
3459	PD	PROM1	ENST00000447510	c.1117C>T	p.Arg373Cys	het	-	16.9	AD	+	+	PS1, PM2
3526	PD	PRPH2	ENST00000230381	c.246C>A	p.Cys82*	het	-	36.0	AD			PM2, PM4
3672	STGD1	CRX	ENST00000221996	c.262A>G	p.Lys88Glu	het	-	26.9	AD		+ °	PM2, PM5
3746	STGD1	PRPH2#	ENST00000230381	c.749 769delinsCA TGA	p.Cys250SerfsTer8	het	-	0.0	AD	+	+ °	PM2, PM4
3830	BEM	CRX	ENST00000221996	c.268C>T	p.Arg90Trp	het	1.3E-04	34.0	AD		+	PS1
3922	STGD1	PROM1	ENST00000447510	c.303+1G>A	p.?	het	0	24.6	AD			PM1, PP4
4246	PD	PROM1	ENST00000447510	c.303+2T>C	p.?	het	-	23.8	AD			PM1, PP4
4337	STGD1	PROM1	ENST00000447510	c.400C>T	p.Arg134Cys	het	3.6E-05	35.0	AD	+		PM3, PP3
4369	PD	PRPH2	ENST00000230381	c.582–1G>A	p?	het	-	27.1	AD		+	PS1
4416	BEM	CRX	ENST00000221996	c.258G>T	p.Trp86Cys	het	-	27.5	AD			PM1, PM2
4539	CRD	PROM1	ENST00000447510	c.1157T>A	p.Leu386*	het	-	35.0	AR	+	+	PS1,PM3
		PROM1	ENST00000447510	c.1557C>A	p.Tyr519*	het	7.0E-05	35.0	AR	+	+	PS1, PM3
4548	BEM	CRX	ENST00000221996	c.206G>A	p.Arg69His	het	0	27.7	AD	-		PM1, PM2
4619	CRD	CERKL	ENST00000339098	c.847C>T	p.Arg283*	hom	5.5E-04	28.6	AR		+	PS1, PM2,
4645	CRD	CERKL	ENST00000339098	c.847C>T	p.Arg283*	hom	5.5E-04	28.6	AR		+	PS1, PM2,

Abbreviations: STGD1, Stargardt disease; CRD, Cone-rod dystrophy, BEM, bull’s eye maculopathy; PD, Pattern dystrophy; MD, Macular dystrophy; RP, retinitis pigmentosa; het, heterozygous; hom, homozygous; gnomAD, The Genome Aggregation Database (http://gnomad.broadinstitute.org/); MAF, minor allele frequency; CADD, Combined Annotation Dependent Depletion (http://cadd.gs.washington.edu/home); AD, autosomal dominant; AR, autosomal recessive.

^*None of these variants were observed in study controls

^#Predicted change resulting from three frameshift variants on the same allele.

^°New pathogenic variants at the same amino acid position as previously reported.

^†MAF in the non-Finnish European population as all presented cases are of non-Finnish European ancestry and represent the highest MAF except for 2 variants labeled as 0. The PROM1 variant c.303+1G>A is detected once in the “Other” population and the CRX p.Arg69His is detected once in the African population. Variants absent from gnomAD database are indicated by a dash (−).

^‡CADD score > 20 suggests pathogenicity

^aBased on Guidelines for interpretation of sequence variants. Richards et al., Genet Med. 2015