Table 1.

Prioritized genetic findings in the oCCDD cohort

Gene	Variant	ACMG/AMP/ ClinGen Classification	Category	Pedigrees	Diagnosis
ACMG/AMP/ClinGen-Pathogenic and likely pathogenic variants
KIF21A	NP_001166935.1: p.(Arg954Trp)	P	[oCCDD+, Syndrome+/−]	198; ENG_AWA	Isolated sporadic CFEOM; isolated familial CFEOM
ROBO3	NP_071765.2: p.(Arg191ProfsTer61)	P	[oCCDD+, Syndrome+/−]	193	Syndromic sporadic HGP
TUBB3	NP_006077.2: p.(Asp417Asn)	P	[oCCDD+, Syndrome+/−]	ENG_ABW	Isolated sporadic CFEOM
TUBB3	NP_006077.2: p.(Gly71Arg)	P	[oCCDD+, Syndrome+/−]	81	Syndromic sporadic CFEOM
ACTB	NP_001092.1: p.(Ser348Leu)	P	[oCCDD(+), Syndrome+]	27	Syndromic sporadic congenital ptosis
BBS1	NP_078925.3: p.(Met390Arg)	P	[oCCDD(+), Syndrome+]	71	Syndromic sporadic CFEOM
BBS1	NP_078925.3: p.(Glu549Ter)	P	[oCCDD(+), Syndrome+]	71	Syndromic sporadic CFEOM
DMD	NP_003997.2: p.(Leu3485ArgfsTer11)	P	[oCCDD(+), Syndrome+]	227	Syndromic familial Brown syndrome
EBF3	NP_001362309.1: p.(Arg312Ter)	P	[oCCDD(+), Syndrome+]	42	Syndromic sporadic CN4-palsy
EBF3	NC_000014.9: g.53949639_56297420del	P	[oCCDD(+), Syndrome+]	233; 131	Syndromic sporadic DRS; syndromic sporadic DRS
FGD1	NP_004454.2: p.(Leu177ThrfsTer40)	P	[oCCDD(+), Syndrome+]	ENG_1894	Syndromic sporadic CFEOM
GCH1	NC_000014.9: g.53949639_56297420del	P	[oCCDD(+), Syndrome+]	ENG_BS	Syndromic familial congenital ptosis
HDAC8	NC_000023.11: g.72570670_72613916del	P	[oCCDD(+), Syndrome+]	13	Syndromic sporadic congenital ptosis
KIAA0586	NP_001316872.1: p.(Arg131LysfsTer4)	P	[oCCDD(+), Syndrome+]	ENG_AGZ	Syndromic sporadic CN6-palsy
KIFBP	NP_056449.1: p.(Ser200Ter)	P	[oCCDD(+), Syndrome+]	239	Syndromic familial CFEOM
KMT2D	NP_003473.3: p.(Arg5021Ter)	P	[oCCDD(+), Syndrome+]	128	Syndromic sporadic Brown syndrome
MED13	NP_005112.2:p.?	P	[oCCDD(+), Syndrome+]	61	Syndromic sporadic DRS
PHOX2B	NP_003915.2: p.(Ala256_Ala260dup)	P	[oCCDD(+), Syndrome+]	242	Syndromic sporadic MGJWS(+)ptosis
PIEZO2	NP_001365112.1: p.(Arg2799His)	P	[oCCDD(+), Syndrome+]	ENG_BAG	Syndromic sporadic CCDD-NOS
PTPN11	NP_002825.3: p.(Leu261Phe)	P	[oCCDD(+), Syndrome+]	ENG_CKA	Syndromic familial CCDD-NOS
TRPV4	NP_067638.3: p.(Arg269His)	P	[oCCDD(+), Syndrome+]	4	Syndromic sporadic CCDD-NOS
ZC4H2	NP_061154.1: p.(Lys81AsnfsTer6)	P	[oCCDD(+), Syndrome+]	14416	Syndromic sporadic DRS
ARMC4	NP_060546.2: p.(Ser892Ter)	P	[oCCDD-, Syndrome+]	269	Syndromic familial CFEOM
CDK13	NP_003709.3: p.(Gly717Arg)	P	[oCCDD-, Syndrome+]	ENG_2270	Syndromic sporadic DRS
FOXG1	NP_005240.3: p.(Gln86ArgfsTer106)	P	[oCCDD-, Syndrome+]	ENG_CHA	Syndromic sporadic CFEOM
GJB2	NP_003995.2: p.(Gly12ValfsTer2)	P	[oCCDD-, Syndrome+]	238	Syndromic familial DRS
SCN1A	NP_001159435.1: p.(Ile1545Val)	P	[oCCDD-, Syndrome+]	93	Syndromic sporadic DRS
TGFB2	NP_003229.1: p.(Arg299Trp)	P	[oCCDD-, Syndrome+]	ENG_FI	Isolated familial CCDD-NOS
TUBA1A	NP_006000.2: p.(His406Asp)	P	[oCCDD-, Syndrome+]	3819	Syndromic sporadic CFEOM
FOXL2	NP_075555.1: p.(Leu75Phe)	P	[Misdiagnoses]	ENG_JP	Isolated familial congenital ptosis
ARMC9	NP_001339683.2: p.(Thr293=)	LP	[oCCDD(+), Syndrome+]	269, 270	Syndromic familial CFEOM; syndromic sporadic CFEOM
DYRK1A	NP_001334650.1: p.(Leu66Ter)	LP	[oCCDD(+), Syndrome+]	26	Syndromic sporadic DRS
FBN1	NP_000129.3: p.(Cys1053Tyr)	LP	[oCCDD(+), Syndrome+]	ENG_ACR	Syndromic sporadic HGP
KIAA0586	NP_001316872.1: p.(Gln263Ter)	LP	[oCCDD(+), Syndrome+]	ENG_AGZ	Syndromic sporadic CN6-palsy
KIFBP	NP_056449.1: p.(Ala362SerfsTer8)	LP	[oCCDD(+), Syndrome+]	239	Syndromic familial CFEOM
MED13	NP_005112.2: p.(Leu1188IlefsTer9)	LP	[oCCDD(+), Syndrome+]	62	Syndromic sporadic DRS
POGZ	NP_055915.2: p.(Phe836LeufsTer18)	LP	[oCCDD(+), Syndrome+]	ENG_CMO	Syndromic sporadic congenital ptosis
TGFBR2	NP_003233.4: p.(Arg460Leu)	LP	[oCCDD(+), Syndrome+]	ENG_ADU	Syndromic sporadic HGP
ZC4H2	NP_061154.1: p.(Arg198Trp)	LP	[oCCDD(+), Syndrome+]	257	Syndromic sporadic DRS
ZNF462	NP_067047.4: p.(Arg255Ter)	LP	[oCCDD(+), Syndrome+]	4817	Syndromic familial congenital ptosis
ZNF462	NP_067047.4: p.(Tyr1704Ter)	LP	[oCCDD(+), Syndrome+]	ENG_AHO	Syndromic familial CFEOM
CEP83	NP_057206.2: p.(Glu530Ter)	LP	[oCCDD-, Syndrome+]	ENG_AZW	Syndromic sporadic CFEOM
RYR1	NP_000531.2: p.(Arg3772Trp)	LP	[Misdiagnoses]	ENG_AKG	Syndromic sporadic CFEOM
TWIST1	NP_000465.1: p.(Ala129_Ile135dup)	LP	[Misdiagnoses]	ENG_0640	Syndromic familial congenital ptosis
Select ACMG/AMP/ClinGen-variants of uncertain significance with highest supportive evidence
CHN1	NP_001813.1: p.(Ala27Gly)	VUS	[oCCDD+, Syndrome+/−]	ENG_1580	Isolated sporadic DRS
CHN1	NP_001813.1: p.(Tyr21Cys)	VUS	[oCCDD+, Syndrome+/−]	ENG_BBG	Syndromic sporadic CN6-palsy
MAFB	NP_005452.2: p.(Glu223Lys)	VUS	[oCCDD+, Syndrome+/−]	232	Isolated familial DRS
PHOX2A	NP_005160.2: p.(Trp137Cys)	VUS	[oCCDD+, Syndrome+/−]	160	Syndromic sporadic CFEOM
SALL4	NC_000020.11: g.51783476_51785034del	VUS	[oCCDD+, Syndrome+/−]	DQ	Syndromic sporadic DRS
ARMC9	NP_001339683.2: p.(Arg343Ser)	VUS	[oCCDD(+), Syndrome+]	ENG_COX	Syndromic sporadic CFEOM
COL25A1	NP_942014.1: p.(Gly400Arg)	VUS	[oCCDD(+), Syndrome+]	5620	Syndromic sporadic CFEOM
ECEL1	NP_004817.2: p.(Cys772Arg)	VUS	[oCCDD(+), Syndrome+]	223	Syndromic familial DRS
KIF21B	NP_001239031.1: p.(Phe354Ser)	VUS	[oCCDD(+), Syndrome+]	ENG_FR	Syndromic sporadic CFEOM
TUBB6	NP_115914.1: p.(Glu410Lys)	VUS	[oCCDD(+), Syndrome+]	ENG_CML	Syndromic familial congenital ptosis
MACF1	NC_000001.11: g.39428731_39468326del	VUS	[oCCDD-, Syndrome+]	9818	Syndromic sporadic CN6-palsy
TUBA1A	NP_006000.2: p.(Ser379Asn)	VUS	[oCCDD-, Syndrome+]	170	Syndromic sporadic DRS
TUBA4A	NP_005991.1: p.(Arg390His)	VUS	[oCCDD-, Syndrome-]	ENG_IM	Isolated sporadic congenital ptosis
CHRNE	NP_000071.1: p.(Ile194Thr)	VUS	[Misdiagnoses]	ENG_2044	Syndromic sporadic congenital ptosis