PanelApp

Activity

Filter

Cancel
Date Panel Item Activity
3000 actions
Prepair 1000+ v1.2146 TSPYL1 Seb Lunke Tag review was removed from gene: TSPYL1.
Prepair 1000+ v1.2146 TTN Seb Lunke Tag for review was removed from gene: TTN.
Prepair 1000+ v1.2146 CERKL Seb Lunke Tag for review was removed from gene: CERKL.
Prepair 1000+ v1.2146 CLN3 Seb Lunke Tag for review was removed from gene: CLN3.
Prepair 1000+ v1.2146 LRSAM1 Seb Lunke Tag for review was removed from gene: LRSAM1.
Prepair 1000+ v1.2146 NCF1 Seb Lunke Tag for review was removed from gene: NCF1.
Prepair 1000+ v1.2146 RARB Seb Lunke Tag for review was removed from gene: RARB.
Prepair 1000+ v1.2146 SLC9A3 Seb Lunke Tag for review was removed from gene: SLC9A3.
Prepair 1000+ v1.2146 FYCO1 Zornitza Stark Tag review was removed from gene: FYCO1.
Prepair 1000+ v1.2146 PRICKLE1 Seb Lunke Tag for review was removed from gene: PRICKLE1.
Prepair 1000+ v1.2146 TSPYL1 Seb Lunke Classified gene: TSPYL1 as Green List (high evidence)
Prepair 1000+ v1.2146 TSPYL1 Seb Lunke Added comment: Comment on list classification: Assessed, meets conditions as additional non-founder variants identified
Prepair 1000+ v1.2146 TSPYL1 Seb Lunke Gene: tspyl1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2145 B9D1 Zornitza Stark Tag for review was removed from gene: B9D1.
Prepair 1000+ v1.2145 ADPRHL2 Zornitza Stark Tag for review was removed from gene: ADPRHL2.
Prepair 1000+ v1.2145 ACY1 Zornitza Stark Tag for review was removed from gene: ACY1.
Prepair 1000+ v1.2145 PEX19 Lilian Downie Classified gene: PEX19 as Green List (high evidence)
Prepair 1000+ v1.2145 PEX19 Lilian Downie Gene: pex19 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2145 SCO1 Seb Lunke Classified gene: SCO1 as Green List (high evidence)
Prepair 1000+ v1.2145 SCO1 Seb Lunke Gene: sco1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2144 PIEZO1 Zornitza Stark Marked gene: PIEZO1 as ready
Prepair 1000+ v1.2144 PIEZO1 Zornitza Stark Gene: piezo1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2144 SCO1 Seb Lunke Tag for review was removed from gene: SCO1.
Prepair 1000+ v1.2144 PIEZO1 Zornitza Stark Classified gene: PIEZO1 as Green List (high evidence)
Prepair 1000+ v1.2144 PIEZO1 Zornitza Stark Gene: piezo1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2143 PIEZO1 Zornitza Stark Tag for review was removed from gene: PIEZO1.
Prepair 1000+ v1.2143 PDHX Zornitza Stark Classified gene: PDHX as Green List (high evidence)
Prepair 1000+ v1.2143 PDHX Zornitza Stark Gene: pdhx has been classified as Green List (High Evidence).
Prepair 1000+ v1.2143 OTULIN Seb Lunke Classified gene: OTULIN as Green List (high evidence)
Prepair 1000+ v1.2143 OTULIN Seb Lunke Gene: otulin has been classified as Green List (High Evidence).
Prepair 1000+ v1.2142 PDHX Zornitza Stark Tag for review was removed from gene: PDHX.
Prepair 1000+ v1.2142 OTULIN Seb Lunke Tag for review was removed from gene: OTULIN.
Prepair 1000+ v1.2142 MTPAP Zornitza Stark Classified gene: MTPAP as Green List (high evidence)
Prepair 1000+ v1.2142 MTPAP Zornitza Stark Gene: mtpap has been classified as Green List (High Evidence).
Prepair 1000+ v1.2142 CHMP1A Lilian Downie Classified gene: CHMP1A as Green List (high evidence)
Prepair 1000+ v1.2142 CHMP1A Lilian Downie Gene: chmp1a has been classified as Green List (High Evidence).
Prepair 1000+ v1.2141 MTPAP Zornitza Stark Tag for review was removed from gene: MTPAP.
Prepair 1000+ v1.2141 CHMP1A Lilian Downie Tag for review was removed from gene: CHMP1A.
Prepair 1000+ v1.2141 APC2 Seb Lunke Classified gene: APC2 as Green List (high evidence)
Prepair 1000+ v1.2141 APC2 Seb Lunke Gene: apc2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2140 APC2 Seb Lunke Tag for review was removed from gene: APC2.
Prepair 1000+ v1.2140 AMN Zornitza Stark Marked gene: AMN as ready
Prepair 1000+ v1.2140 AMN Zornitza Stark Added comment: Comment when marking as ready: Treatable, relatively mild disorder, not suitable for inclusion on a reproductive carrier screen.
Prepair 1000+ v1.2140 AMN Zornitza Stark Gene: amn has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2140 AMN Zornitza Stark Classified gene: AMN as Red List (low evidence)
Prepair 1000+ v1.2140 AMN Zornitza Stark Gene: amn has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2139 AMN Zornitza Stark Tag for review was removed from gene: AMN.
Prepair 1000+ v1.2139 AGTR1 Zornitza Stark Classified gene: AGTR1 as Green List (high evidence)
Prepair 1000+ v1.2139 AGTR1 Zornitza Stark Gene: agtr1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2138 YIF1B Seb Lunke Tag for review was removed from gene: YIF1B.
Prepair 1000+ v1.2138 YIF1B Seb Lunke Classified gene: YIF1B as Green List (high evidence)
Prepair 1000+ v1.2138 YIF1B Seb Lunke Gene: yif1b has been classified as Green List (High Evidence).
Prepair 1000+ v1.2137 AGTR1 Zornitza Stark Tag for review was removed from gene: AGTR1.
Prepair 1000+ v1.2137 UQCRC2 Zornitza Stark Marked gene: UQCRC2 as ready
Prepair 1000+ v1.2137 UQCRC2 Zornitza Stark Added comment: Comment when marking as ready: Borderline gene-disease association, keep Amber in the screening context.
Prepair 1000+ v1.2137 UQCRC2 Zornitza Stark Gene: uqcrc2 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.2137 UQCRC2 Zornitza Stark Publications for gene: UQCRC2 were set to
Prepair 1000+ v1.2136 UQCRC2 Zornitza Stark Classified gene: UQCRC2 as Amber List (moderate evidence)
Prepair 1000+ v1.2136 UQCRC2 Zornitza Stark Gene: uqcrc2 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.2135 UQCRC2 Zornitza Stark Tag for review was removed from gene: UQCRC2.
Prepair 1000+ v1.2135 TRAPPC6B Seb Lunke Classified gene: TRAPPC6B as Green List (high evidence)
Prepair 1000+ v1.2135 TRAPPC6B Seb Lunke Gene: trappc6b has been classified as Green List (High Evidence).
Prepair 1000+ v1.2134 TP53RK Lilian Downie Classified gene: TP53RK as Green List (high evidence)
Prepair 1000+ v1.2134 TP53RK Lilian Downie Gene: tp53rk has been classified as Green List (High Evidence).
Prepair 1000+ v1.2133 TRAPPC6B Seb Lunke Tag for review was removed from gene: TRAPPC6B.
Prepair 1000+ v1.2133 TP53RK Lilian Downie Tag for review was removed from gene: TP53RK.
Prepair 1000+ v1.2133 TPRKB Zornitza Stark Marked gene: TPRKB as ready
Prepair 1000+ v1.2133 TPRKB Zornitza Stark Gene: tprkb has been classified as Green List (High Evidence).
Prepair 1000+ v1.2133 TPRKB Zornitza Stark Publications for gene: TPRKB were set to 30053862; 28805828
Prepair 1000+ v1.2132 TPRKB Zornitza Stark Classified gene: TPRKB as Green List (high evidence)
Prepair 1000+ v1.2132 TPRKB Zornitza Stark Gene: tprkb has been classified as Green List (High Evidence).
Prepair 1000+ v1.2131 TPRKB Zornitza Stark Tag for review was removed from gene: TPRKB.
Prepair 1000+ v1.2131 TBC1D20 Lilian Downie Tag for review was removed from gene: TBC1D20.
Prepair 1000+ v1.2131 PKD1L1 Zornitza Stark Marked gene: PKD1L1 as ready
Prepair 1000+ v1.2131 PKD1L1 Zornitza Stark Gene: pkd1l1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2131 PKD1L1 Zornitza Stark Tag for review was removed from gene: PKD1L1.
Prepair 1000+ v1.2131 TBC1D20 Lilian Downie Classified gene: TBC1D20 as Green List (high evidence)
Prepair 1000+ v1.2131 TBC1D20 Lilian Downie Gene: tbc1d20 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2130 PKD1L1 Zornitza Stark reviewed gene: PKD1L1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Heterotaxy, visceral, 8, autosomal MIM#617205; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2130 MFRP Zornitza Stark Classified gene: MFRP as Green List (high evidence)
Prepair 1000+ v1.2130 MFRP Zornitza Stark Gene: mfrp has been classified as Green List (High Evidence).
Prepair 1000+ v1.2129 MFRP Zornitza Stark Tag for review was removed from gene: MFRP.
Prepair 1000+ v1.2129 ITGA3 Lilian Downie Classified gene: ITGA3 as Green List (high evidence)
Prepair 1000+ v1.2129 ITGA3 Lilian Downie Gene: itga3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2128 ISCA1 Zornitza Stark Marked gene: ISCA1 as ready
Prepair 1000+ v1.2128 ISCA1 Zornitza Stark Gene: isca1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2128 ISCA1 Zornitza Stark Classified gene: ISCA1 as Green List (high evidence)
Prepair 1000+ v1.2128 ISCA1 Zornitza Stark Gene: isca1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2127 ISCA1 Zornitza Stark Tag for review was removed from gene: ISCA1.
Prepair 1000+ v1.2127 IMPG2 Zornitza Stark Marked gene: IMPG2 as ready
Prepair 1000+ v1.2127 IMPG2 Zornitza Stark Gene: impg2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2127 IMPG2 Zornitza Stark Publications for gene: IMPG2 were set to
Prepair 1000+ v1.2126 IMPG2 Zornitza Stark Classified gene: IMPG2 as Green List (high evidence)
Prepair 1000+ v1.2126 IMPG2 Zornitza Stark Gene: impg2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2125 IMPG2 Zornitza Stark Tag for review was removed from gene: IMPG2.
Prepair 1000+ v1.2125 HBA2 Seb Lunke Tag SV/CNV tag was added to gene: HBA2.
Prepair 1000+ v1.2125 HBA2 Zornitza Stark Marked gene: HBA2 as ready
Prepair 1000+ v1.2125 HBA2 Zornitza Stark Added comment: Comment when marking as ready: Discussed again: remains technically challenging therefore not suitable for inclusion. Other screening publicly available in pregnancy.
Prepair 1000+ v1.2125 HBA2 Zornitza Stark Gene: hba2 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2125 HBA2 Zornitza Stark Tag for review was removed from gene: HBA2.
Prepair 1000+ v1.2125 HBA1 Seb Lunke Tag SV/CNV tag was added to gene: HBA1.
Prepair 1000+ v1.2125 HBA1 Zornitza Stark Marked gene: HBA1 as ready
Prepair 1000+ v1.2125 HBA1 Zornitza Stark Added comment: Comment when marking as ready: Discussed again: remains technically challenging therefore not suitable for inclusion. Other screening publicly available in pregnancy.
Prepair 1000+ v1.2125 HBA1 Zornitza Stark Gene: hba1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2125 GTPBP2 Lilian Downie Classified gene: GTPBP2 as Green List (high evidence)
Prepair 1000+ v1.2125 GTPBP2 Lilian Downie Gene: gtpbp2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2124 HBA1 Zornitza Stark Tag for review was removed from gene: HBA1.
Prepair 1000+ v1.2124 GTPBP2 Lilian Downie Tag for review was removed from gene: GTPBP2.
Prepair 1000+ v1.2124 IGHM Seb Lunke Classified gene: IGHM as Green List (high evidence)
Prepair 1000+ v1.2124 IGHM Seb Lunke Added comment: Comment on list classification: Caution: Gene has annotation issues due to lack of refseq transcript annotation and maybe missed by some analysis pipelines. Checked ok for prepair+
Prepair 1000+ v1.2124 IGHM Seb Lunke Gene: ighm has been classified as Green List (High Evidence).
Prepair 1000+ v1.2123 FITM2 Zornitza Stark Marked gene: FITM2 as ready
Prepair 1000+ v1.2123 FITM2 Zornitza Stark Gene: fitm2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2123 FITM2 Zornitza Stark Classified gene: FITM2 as Green List (high evidence)
Prepair 1000+ v1.2123 FITM2 Zornitza Stark Gene: fitm2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2122 FITM2 Zornitza Stark Tag for review was removed from gene: FITM2.
Prepair 1000+ v1.2122 CSMD1 Lilian Downie Classified gene: CSMD1 as Green List (high evidence)
Prepair 1000+ v1.2122 CSMD1 Lilian Downie Gene: csmd1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2121 CSMD1 Lilian Downie Tag for review was removed from gene: CSMD1.
Prepair 1000+ v1.2121 COG5 Zornitza Stark Classified gene: COG5 as Green List (high evidence)
Prepair 1000+ v1.2121 COG5 Zornitza Stark Gene: cog5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2120 COG5 Zornitza Stark Tag for review was removed from gene: COG5.
Prepair 1000+ v1.2120 CHM Zornitza Stark Marked gene: CHM as ready
Prepair 1000+ v1.2120 CHM Zornitza Stark Added comment: Comment when marking as ready: Not suitable for reproductive carrier screening.
Prepair 1000+ v1.2120 CHM Zornitza Stark Gene: chm has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2120 BCAP31 Lilian Downie Classified gene: BCAP31 as Green List (high evidence)
Prepair 1000+ v1.2120 BCAP31 Lilian Downie Gene: bcap31 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2119 BCAP31 Lilian Downie Tag for review was removed from gene: BCAP31.
Prepair 1000+ v1.2119 CHM Zornitza Stark Tag for review was removed from gene: CHM.
Prepair 1000+ v1.2119 ACY1 Zornitza Stark Classified gene: ACY1 as Green List (high evidence)
Prepair 1000+ v1.2119 ACY1 Zornitza Stark Gene: acy1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2118 TTN Zornitza Stark Phenotypes for gene: TTN were changed from Myopathy, early-onset, with fatal cardiomyopathy, 611705 (3) to TTN-related myopathy MONDO:0100175
Prepair 1000+ v1.2117 XPNPEP3 Lilian Downie Classified gene: XPNPEP3 as Green List (high evidence)
Prepair 1000+ v1.2117 XPNPEP3 Lilian Downie Gene: xpnpep3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2116 TTN Zornitza Stark Publications for gene: TTN were set to
Prepair 1000+ v1.2115 XPNPEP3 Lilian Downie Tag for review was removed from gene: XPNPEP3.
Prepair 1000+ v1.2115 TTN Zornitza Stark Classified gene: TTN as Green List (high evidence)
Prepair 1000+ v1.2115 TTN Zornitza Stark Gene: ttn has been classified as Green List (High Evidence).
Prepair 1000+ v1.2114 TTN Zornitza Stark reviewed gene: TTN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: TTN-related myopathy MONDO:0100175; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2114 TMEM94 Lilian Downie Classified gene: TMEM94 as Green List (high evidence)
Prepair 1000+ v1.2114 TMEM94 Lilian Downie Gene: tmem94 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2113 TMEM94 Lilian Downie Tag for review was removed from gene: TMEM94.
Prepair 1000+ v1.2113 POLA1 Zornitza Stark Marked gene: POLA1 as ready
Prepair 1000+ v1.2113 POLA1 Zornitza Stark Added comment: Comment when marking as ready: Inclusion assumes appropriate coverage by capture method (checked for Prepair+)
Prepair 1000+ v1.2113 POLA1 Zornitza Stark Gene: pola1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2113 POLA1 Zornitza Stark Tag for review was removed from gene: POLA1.
Prepair 1000+ v1.2113 POLA1 Zornitza Stark Classified gene: POLA1 as Green List (high evidence)
Prepair 1000+ v1.2113 POLA1 Zornitza Stark Gene: pola1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2112 NTNG2 Lilian Downie Classified gene: NTNG2 as Green List (high evidence)
Prepair 1000+ v1.2112 NTNG2 Lilian Downie Gene: ntng2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2111 NTNG2 Lilian Downie Tag for review was removed from gene: NTNG2.
Prepair 1000+ v1.2111 NCF1 Zornitza Stark Marked gene: NCF1 as ready
Prepair 1000+ v1.2111 NCF1 Zornitza Stark Added comment: Comment when marking as ready: Remains technically challenging, therefore exclude from V2.
Prepair 1000+ v1.2111 NCF1 Zornitza Stark Gene: ncf1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.2111 MOGS Lilian Downie Classified gene: MOGS as Green List (high evidence)
Prepair 1000+ v1.2111 MOGS Lilian Downie Gene: mogs has been classified as Green List (High Evidence).
Prepair 1000+ v1.2110 MOGS Lilian Downie Tag for review was removed from gene: MOGS.
Prepair 1000+ v1.2110 MBTPS1 Zornitza Stark Phenotypes for gene: MBTPS1 were changed from ?Spondyloepiphyseal dysplasia, Kondo-Fu type, MIM #618392 to Spondyloepiphyseal dysplasia, Kondo-Fu type MIM#618392
Prepair 1000+ v1.2109 MBTPS1 Zornitza Stark Classified gene: MBTPS1 as Green List (high evidence)
Prepair 1000+ v1.2109 MBTPS1 Zornitza Stark Gene: mbtps1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2108 DYNC1I2 Seb Lunke Classified gene: DYNC1I2 as Green List (high evidence)
Prepair 1000+ v1.2108 DYNC1I2 Seb Lunke Gene: dync1i2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2107 DYNC1I2 Seb Lunke Tag for review was removed from gene: DYNC1I2.
Prepair 1000+ v1.2107 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Visceral neuropathy, familial, 1, autosomal recessive MIM#243180 to Visceral neuropathy, familial, 1, autosomal recessive MIM#243180; Lethal congenital contractural syndrome 2 MIM#607598
Prepair 1000+ v1.2106 CSTB Seb Lunke Tag for review was removed from gene: CSTB.
Prepair 1000+ v1.2106 ERBB3 Zornitza Stark Classified gene: ERBB3 as Green List (high evidence)
Prepair 1000+ v1.2106 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2105 CERKL Lilian Downie commented on gene: CERKL
Prepair 1000+ v1.2105 B9D1 Zornitza Stark Classified gene: B9D1 as Green List (high evidence)
Prepair 1000+ v1.2105 B9D1 Zornitza Stark Gene: b9d1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2104 ADPRHL2 Seb Lunke Classified gene: ADPRHL2 as Green List (high evidence)
Prepair 1000+ v1.2104 ADPRHL2 Seb Lunke Gene: adprhl2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2103 VKORC1 Zornitza Stark Marked gene: VKORC1 as ready
Prepair 1000+ v1.2103 VKORC1 Zornitza Stark Added comment: Comment when marking as ready: Treatable condition, vast majority receive Vitamin K at birth; not in scope for panel.
Prepair 1000+ v1.2103 VKORC1 Zornitza Stark Gene: vkorc1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2103 VKORC1 Zornitza Stark Phenotypes for gene: VKORC1 were changed from Vitamin K-dependent clotting factors, combined deficiency of, 2, 607473 (3) to Vitamin K-dependent clotting factors, combined deficiency of, 2, MIM#607473
Prepair 1000+ v1.2102 VKORC1 Zornitza Stark Publications for gene: VKORC1 were set to
Prepair 1000+ v1.2101 VKORC1 Zornitza Stark Classified gene: VKORC1 as Red List (low evidence)
Prepair 1000+ v1.2101 VKORC1 Zornitza Stark Gene: vkorc1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2100 RNU4ATAC Lilian Downie commented on gene: RNU4ATAC
Prepair 1000+ v1.2100 VKORC1 Zornitza Stark Tag for review was removed from gene: VKORC1.
Infertility and Recurrent Pregnancy Loss v0.63 PATL2 Jasmine Chew edited their review of gene: PATL2: Changed phenotypes: Oocyte/zygote/embryo maturation arrest 4, MIM# 617743
Prepair 1000+ v1.2100 RNU4ATAC Lilian Downie Tag for review was removed from gene: RNU4ATAC.
Prepair 1000+ v1.2100 SURF1 Zornitza Stark Tag for review was removed from gene: SURF1.
Prepair 1000+ v1.2100 SLC9A3 Seb Lunke Classified gene: SLC9A3 as Amber List (moderate evidence)
Prepair 1000+ v1.2100 SLC9A3 Seb Lunke Gene: slc9a3 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.2099 RCBTB1 Zornitza Stark Marked gene: RCBTB1 as ready
Prepair 1000+ v1.2099 RCBTB1 Zornitza Stark Added comment: Comment when marking as ready: Currently, onset appears to mostly in adulthood. Demote and review in the future re new reports with earlier onset.
Prepair 1000+ v1.2099 RCBTB1 Zornitza Stark Gene: rcbtb1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.2099 RCBTB1 Zornitza Stark Phenotypes for gene: RCBTB1 were changed from Retinal dystrophy with or without extraocular anomalies, 617175 (3), Autosomal recessive to Retinal dystrophy with or without extraocular anomalies (MIM#617175)
Prepair 1000+ v1.2098 RCBTB1 Zornitza Stark Publications for gene: RCBTB1 were set to
Prepair 1000+ v1.2097 RCBTB1 Zornitza Stark Classified gene: RCBTB1 as Amber List (moderate evidence)
Prepair 1000+ v1.2097 RCBTB1 Zornitza Stark Gene: rcbtb1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.2096 RCBTB1 Zornitza Stark Tag for review was removed from gene: RCBTB1.
Prepair 1000+ v1.2096 RARB Seb Lunke Classified gene: RARB as Amber List (moderate evidence)
Prepair 1000+ v1.2096 RARB Seb Lunke Added comment: Comment on list classification: Insufficient evidence for recessive disease
Prepair 1000+ v1.2096 RARB Seb Lunke Gene: rarb has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.2095 PRICKLE1 Zornitza Stark Marked gene: PRICKLE1 as ready
Prepair 1000+ v1.2095 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2095 PRICKLE1 Zornitza Stark Phenotypes for gene: PRICKLE1 were changed from Epilepsy, progressive myoclonic 1B, 612437 (3) to Epilepsy, progressive myoclonic 1B, MIM# 612437
Prepair 1000+ v1.2094 PRICKLE1 Zornitza Stark Classified gene: PRICKLE1 as Red List (low evidence)
Prepair 1000+ v1.2094 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2093 LRSAM1 Seb Lunke Classified gene: LRSAM1 as Amber List (moderate evidence)
Prepair 1000+ v1.2093 LRSAM1 Seb Lunke Added comment: Comment on list classification: Insufficient evidence for recessive
Prepair 1000+ v1.2093 LRSAM1 Seb Lunke Gene: lrsam1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.2092 LIPC Zornitza Stark Marked gene: LIPC as ready
Prepair 1000+ v1.2092 LIPC Zornitza Stark Gene: lipc has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2092 LIPC Zornitza Stark Phenotypes for gene: LIPC were changed from Hepatic lipase deficiency, 614025 (3) to Hepatic lipase deficiency, MIM# 614025
Prepair 1000+ v1.2091 LIPC Zornitza Stark Tag for review was removed from gene: LIPC.
Prepair 1000+ v1.2091 LIPC Zornitza Stark Classified gene: LIPC as Red List (low evidence)
Prepair 1000+ v1.2091 LIPC Zornitza Stark Gene: lipc has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2090 LIPC Zornitza Stark edited their review of gene: LIPC: Changed rating: RED
Prepair 1000+ v1.2090 LCAT Lilian Downie Classified gene: LCAT as Red List (low evidence)
Prepair 1000+ v1.2090 LCAT Lilian Downie Added comment: Comment on list classification: Adult onset
Prepair 1000+ v1.2090 LCAT Lilian Downie Gene: lcat has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2089 LCAT Lilian Downie Tag for review was removed from gene: LCAT.
Prepair 1000+ v1.2089 HPD Zornitza Stark Tag for review was removed from gene: HPD.
Prepair 1000+ v1.2089 HBB Zornitza Stark Marked gene: HBB as ready
Prepair 1000+ v1.2089 HBB Zornitza Stark Gene: hbb has been classified as Green List (High Evidence).
Prepair 1000+ v1.2089 HBB Zornitza Stark Phenotypes for gene: HBB were changed from Thalassemias, beta-, 613985 (3) to Thalassemias, beta-, 613985; Sickle cell anaemia, MIM# 603903
Prepair 1000+ v1.2088 CSTB Seb Lunke Tag STR tag was added to gene: CSTB.
Prepair 1000+ v1.2088 HBB Zornitza Stark Tag for review was removed from gene: HBB.
Prepair 1000+ v1.2088 GNE Lilian Downie Classified gene: GNE as Red List (low evidence)
Prepair 1000+ v1.2088 GNE Lilian Downie Added comment: Comment on list classification: Adult onset
Prepair 1000+ v1.2088 GNE Lilian Downie Gene: gne has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2087 GNE Lilian Downie Tag for review was removed from gene: GNE.
Prepair 1000+ v1.2087 CTSF Zornitza Stark Marked gene: CTSF as ready
Prepair 1000+ v1.2087 CTSF Zornitza Stark Added comment: Comment when marking as ready: Generally adult onset, out of scope for panel.
Prepair 1000+ v1.2087 CTSF Zornitza Stark Gene: ctsf has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2087 CSTB Seb Lunke Classified gene: CSTB as Amber List (moderate evidence)
Prepair 1000+ v1.2087 CSTB Seb Lunke Added comment: Comment on list classification: Common dodecamer repeat accounts for 90% of variants, not detectable
Prepair 1000+ v1.2087 CSTB Seb Lunke Gene: cstb has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.2086 CTSF Zornitza Stark Tag for review was removed from gene: CTSF.
Prepair 1000+ v1.2086 CTSF Zornitza Stark Classified gene: CTSF as Red List (low evidence)
Prepair 1000+ v1.2086 CTSF Zornitza Stark Gene: ctsf has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2085 CLN3 Zornitza Stark Marked gene: CLN3 as ready
Prepair 1000+ v1.2085 CLN3 Zornitza Stark Added comment: Comment when marking as ready: Downgrade to Amber until CNV analysis included.
Prepair 1000+ v1.2085 CLN3 Zornitza Stark Gene: cln3 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.2085 CLN3 Zornitza Stark Classified gene: CLN3 as Amber List (moderate evidence)
Prepair 1000+ v1.2085 CLN3 Zornitza Stark Gene: cln3 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.2084 CLCNKB Zornitza Stark Phenotypes for gene: CLCNKB were changed from Bartter syndrome, type 4b, digenic, 613090 (3) to Bartter syndrome, type 3 MIM#607364
Prepair 1000+ v1.2083 CLCNKB Zornitza Stark Marked gene: CLCNKB as ready
Prepair 1000+ v1.2083 CLCNKB Zornitza Stark Added comment: Comment when marking as ready: Digenic forms out of scope for this panel.
Prepair 1000+ v1.2083 CLCNKB Zornitza Stark Gene: clcnkb has been classified as Green List (High Evidence).
Prepair 1000+ v1.2083 CLCNKB Zornitza Stark Tag for review was removed from gene: CLCNKB.
Prepair 1000+ v1.2083 CCDC8 Zornitza Stark Tag for review was removed from gene: CCDC8.
Prepair 1000+ v1.2083 CHMP1A Zornitza Stark Tag for review tag was added to gene: CHMP1A.
Prepair 1000+ v1.2083 BRIP1 Zornitza Stark Marked gene: BRIP1 as ready
Prepair 1000+ v1.2083 BRIP1 Zornitza Stark Added comment: Comment when marking as ready: Other FA genes not included in panel.
Prepair 1000+ v1.2083 BRIP1 Zornitza Stark Gene: brip1 has been removed from the panel.
Prepair 1000+ v1.2083 BRIP1 Zornitza Stark Tag for review tag was added to gene: BRIP1.
Prepair 1000+ v1.2083 AMN Zornitza Stark Tag for review tag was added to gene: AMN.
Prepair 1000+ v1.2083 TRAPPC12 Zornitza Stark Marked gene: TRAPPC12 as ready
Prepair 1000+ v1.2083 TRAPPC12 Zornitza Stark Added comment: Comment when marking as ready: Upgrade to Green in V2.
Prepair 1000+ v1.2083 TRAPPC12 Zornitza Stark Gene: trappc12 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2083 TBC1D20 Zornitza Stark Marked gene: TBC1D20 as ready
Prepair 1000+ v1.2083 TBC1D20 Zornitza Stark Added comment: Comment when marking as ready: Upgrade to Green in V2.
Prepair 1000+ v1.2083 TBC1D20 Zornitza Stark Gene: tbc1d20 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2083 TBC1D20 Zornitza Stark Tag for review tag was added to gene: TBC1D20.
Prepair 1000+ v1.2083 OPN1LW Zornitza Stark Marked gene: OPN1LW as ready
Prepair 1000+ v1.2083 OPN1LW Zornitza Stark Gene: opn1lw has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2083 OPN1LW Zornitza Stark Publications for gene: OPN1LW were set to
Prepair 1000+ v1.2082 SLC39A4 Zornitza Stark Marked gene: SLC39A4 as ready
Prepair 1000+ v1.2082 SLC39A4 Zornitza Stark Gene: slc39a4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2082 SLC39A4 Zornitza Stark Phenotypes for gene: SLC39A4 were changed from Acrodermatitis enteropathica, 201100 (3) to Acrodermatitis enteropathica, MIM# 201100
Prepair 1000+ v1.2081 SLC39A4 Zornitza Stark Publications for gene: SLC39A4 were set to
Prepair 1000+ v1.2080 SLC39A4 Zornitza Stark reviewed gene: SLC39A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 19370757; Phenotypes: Acrodermatitis enteropathica, MIM# 201100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2080 SLC30A10 Zornitza Stark Marked gene: SLC30A10 as ready
Prepair 1000+ v1.2080 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2080 SLC30A10 Zornitza Stark Phenotypes for gene: SLC30A10 were changed from Hypermanganesemia with dystonia, polycythemia, and cirrhosis, 613280 (3) to Hypermanganesemia with dystonia 1, MIM#613280
Prepair 1000+ v1.2079 SLC30A10 Zornitza Stark Publications for gene: SLC30A10 were set to
Prepair 1000+ v1.2078 SLC12A5 Zornitza Stark Marked gene: SLC12A5 as ready
Prepair 1000+ v1.2078 SLC12A5 Zornitza Stark Gene: slc12a5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2078 SLC12A5 Zornitza Stark Phenotypes for gene: SLC12A5 were changed from Epileptic encephalopathy, early infantile, 34, 616645 (3), Autosomal recessive to Developmental and epileptic encephalopathy 34 MIM#616645
Prepair 1000+ v1.2077 SLC12A5 Zornitza Stark Publications for gene: SLC12A5 were set to
Prepair 1000+ v1.2076 SEC23B Zornitza Stark Marked gene: SEC23B as ready
Prepair 1000+ v1.2076 SEC23B Zornitza Stark Gene: sec23b has been classified as Green List (High Evidence).
Prepair 1000+ v1.2076 SEC23B Zornitza Stark Phenotypes for gene: SEC23B were changed from Dyserythropoietic anemia, congenital, type II, 224100 (3) to Dyserythropoietic anaemia, congenital, type II MIM#224100
Prepair 1000+ v1.2075 SEC23B Zornitza Stark Publications for gene: SEC23B were set to
Prepair 1000+ v1.2074 SCNN1B Zornitza Stark Marked gene: SCNN1B as ready
Prepair 1000+ v1.2074 SCNN1B Zornitza Stark Gene: scnn1b has been classified as Green List (High Evidence).
Prepair 1000+ v1.2074 SCNN1B Zornitza Stark Phenotypes for gene: SCNN1B were changed from Pseudohypoaldosteronism, type I, 264350 (3) to Pseudohypoaldosteronism, type IB2, autosomal recessive, MIM#620125
Prepair 1000+ v1.2073 SCNN1B Zornitza Stark Publications for gene: SCNN1B were set to
Prepair 1000+ v1.2072 SCN9A Zornitza Stark Marked gene: SCN9A as ready
Prepair 1000+ v1.2072 SCN9A Zornitza Stark Gene: scn9a has been classified as Green List (High Evidence).
Prepair 1000+ v1.2072 SCN9A Zornitza Stark Phenotypes for gene: SCN9A were changed from Insensitivity to pain, congenital, 243000 (3) to Insensitivity to pain, congenital, MIM# 243000
Prepair 1000+ v1.2071 SCN9A Zornitza Stark Publications for gene: SCN9A were set to
Prepair 1000+ v1.2070 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Prepair 1000+ v1.2070 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2070 SAMHD1 Zornitza Stark Phenotypes for gene: SAMHD1 were changed from Aicardi-Goutieres syndrome 5, 612952 (3) to Aicardi-Goutieres syndrome 5, MIM# 612952
Prepair 1000+ v1.2069 SAMHD1 Zornitza Stark reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2069 RRM2B Zornitza Stark Marked gene: RRM2B as ready
Prepair 1000+ v1.2069 RRM2B Zornitza Stark Gene: rrm2b has been classified as Green List (High Evidence).
Prepair 1000+ v1.2069 RRM2B Zornitza Stark Phenotypes for gene: RRM2B were changed from Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075 (3) to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) MIM#612075; Mitochondrial DNA depletion syndrome 8B (MNGIE type) MIM#612075
Prepair 1000+ v1.2068 RRM2B Zornitza Stark reviewed gene: RRM2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) MIM#612075, Mitochondrial DNA depletion syndrome 8B (MNGIE type) MIM#612075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.63 RNF212B Jasmine Chew edited their review of gene: RNF212B: Changed phenotypes: Female and male infertility with recurrent medically assisted reproduction (MAR) failures
Infertility and Recurrent Pregnancy Loss v0.63 RNF212B Jasmine Chew gene: RNF212B was added
gene: RNF212B was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: RNF212B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF212B were set to 40259604; 37124137
Phenotypes for gene: RNF212B were set to Female and male infertility with recurrent medically assisted reproduction (MAR) failures.
Review for gene: RNF212B was set to AMBER
Added comment: Based on available evidence so far, it seems to be affecting Ashkenazi
Jewish population specifically:

i) PMID: 40259604- homozygous stop gained variant p.Arg150Ter in a young Ashkenazi Jewish female with a history of RPL underwent five in vitro fertilization cycles with nearly complete arrest of blastocyst development and ubiquitous aneuploidy of maternal origin in arrested embryos.

ii) PMID: 37124137- homozygous nonsense variant R150X in two brothers of Turkish Jewish descent and one unrelated Ashkenazi Jewish male with oligoasthenotheratozoospermia and infertility who had undergone numerous fertility treatments and failed IVF cycles. Single-cell RNA sequencing data analysis demonstrated expression of the pathogenic variant during various steps of spermatogenesis and consequent severe genomic instability in their sperm and embryos.
Sources: Literature
Pneumothorax v1.1 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Infertility and Recurrent Pregnancy Loss v0.63 PDCD2 Jasmine Chew gene: PDCD2 was added
gene: PDCD2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: PDCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD2 were set to 40208938
Phenotypes for gene: PDCD2 were set to Non-immune hydrops fetalis, MONDO:0009369; Recurrent pregnancy loss susceptibility, MONDO:0000144
Review for gene: PDCD2 was set to AMBER
Added comment: PMID: 40208938- Novel biallelic PDCD2 variants associated with hydrops fetalis and early pregnancy loss in two affected families. Family 1 with RPL had three fetuses with NIHF who were all homozygous for p.(Pro28Ser) in PDCD2, while Family 2 had p.(Pro28Ser) in trans with p.(Arg34Pro) in two fetuses with NIHF. Family 2 was additionally notable for having a healthy child who was homozygous for the reference allele, consistent with appropriate disease segregation with the PDCD2 variants. Functional studies using primary fetal fibroblasts and human cell lines for both variants showed reduced PDCD2 mRNA level in affected patients' fibroblasts, reduced cellular accumulation of mutant proteins with impaired ability to associate with the 40S subunit ribosomal protein uS5, and further depletion of PDCD2 in fibroblast cells severely impacted ribosome biogenesis. It is notable that formation of the PDCD2-uS5 complex was not completely abolished by the patient variants and that rRNA processing was only partially impaired, as indicated by levels of 40S pre-rRNAs. We thus suspect that the PDCD2 pathogenic variants p.(Pro28Ser) and p.(Arg34Pro) are hypomorphic alleles, with a low level of residual function allowing for cellular differentiation and growth to a certain extent.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 MUSK Jasmine Chew gene: MUSK was added
gene: MUSK was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: MUSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MUSK were set to 25612909; 25537362; 31750350; 38566418
Phenotypes for gene: MUSK were set to Fetal akinesia deformation sequence 1, MIM# 208150
Review for gene: MUSK was set to AMBER
Added comment: i) PMID: 25612909- First to report homozygous frameshift variant p.Thr14Asnfs*9 in all affected fetuses with FADS in an affected family which also has two miscarriages. This variant leads to a complete loss of protein expression. Of note, incomplete loss of MuSK function will cause a CMS phenotype, whereas complete loss of function is lethal.

ii) PMID: 25537362- Homozygous missense variant p.Ile575Thr in the intracellular domain of MUSK in 11 out of 14 affected fetuses with lethal FADS (only 11 have DNA available) with a common ancestry from 11 families, suggesting founder effect.

iii) PMID: 31750350- Compound heterozygous variants in an affected fetus with lethal FADS (the mother also had previous abortion due to similarly affected fetus)

iv) Ding et al, 2020 (DOI: 10.22541/au.160097884.45196854)-novel compound heterozygous in a FADS affected fetus (mother also had two previous pregnancies with similarly affected fetuses, terminated)

v) PMID: 38566418- Reviewed previously reported MUSK pathogenic variants (46 patients in total with 29 unique disease-causing variants) appeared in four of the seven MuSK domains, including the Ig1, Frz-like, juxtamembrane, and kinase domains. Homozygous loss-of-function variants resulted in the most severe phenotype (FADS).

Note: Classified as amber since most of the reported cases were TOP rather than IUFD.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 CHRNA1 Jasmine Chew changed review comment from: Spontaneous abortion reported before.

New papers:
i) PMID: 23037934- A novel homozygous p.R254C variant in a family with recurrent fetal loss due to NIHF.

ii) PMID: 18252226- Family CHRNA1-F1 had a family history of spontaneous abortions (IV-2 within the family) and two of the affected fetus (IV-1 stillbirth and IV-3 TOP) carried homozygous R234L.
Sources: Literature; to: Spontaneous abortion reported before.

Other papers:
i) PMID: 23037934- A novel homozygous p.R254C variant in a family with recurrent fetal loss due to NIHF.

ii) PMID: 18252226- Family CHRNA1-F1 had a family history of spontaneous abortions (IV-2 within the family) and two of the affected fetus (IV-1 stillbirth and IV-3 TOP) carried homozygous R234L.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 CHRNA1 Jasmine Chew gene: CHRNA1 was added
gene: CHRNA1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: CHRNA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRNA1 were set to 23037934; 18252226
Phenotypes for gene: CHRNA1 were set to Multiple pterygium syndrome, lethal type, MIM# 253290
Added comment: Spontaneous abortion reported before.

New papers:
i) PMID: 23037934- A novel homozygous p.R254C variant in a family with recurrent fetal loss due to NIHF.

ii) PMID: 18252226- Family CHRNA1-F1 had a family history of spontaneous abortions (IV-2 within the family) and two of the affected fetus (IV-1 stillbirth and IV-3 TOP) carried homozygous R234L.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 TTN Jasmine Chew changed review comment from: i) PMID: 36977548- Reported 10 cases from six unrelated families showing different TTN combinations and four of those cases (F3-iii.1, F6-II.1, F6.ii.3, F6.ii.4) died in utero between 2nd-3rd trimester.
- Quoted that "Probably, we are still missing the most severe end spectrum of titinopathies, as we are used to studying fetuses from late miscarriages or dead infants, while only few investigations are usually performed on early miscarriages. Moreover, prenatal tests often do not include TTN sequencing."

ii)PMID: 38148006- com het p.Arg33743Ter and p.Gln34752Ter in a fetus with with hydrops fetalis and arthrogryposis multiplex congenita, which died in utero in 3rd trimester.

iii) PMID: 29575618- homozygous c.36122delC (p. P12041Lfs*20) variant in 8 members of a consanguineous family affected with a lethal congenital contracture syndrome and among those 8, 3 were IUFD.
Sources: Literature; to: i) PMID: 36977548- Reported 10 cases from six unrelated families showing different TTN combinations and four of those cases (F3-iii.1, F6-II.1, F6.ii.3, F6.ii.4) died in utero between 2nd-3rd trimester.
- Quoted that "Probably, we are still missing the most severe end spectrum of titinopathies, as we are used to studying fetuses from late miscarriages or dead infants, while only few investigations are usually performed on early miscarriages. Moreover, prenatal tests often do not include TTN sequencing."

ii)PMID: 38148006- com het p.Arg33743Ter and p.Gln34752Ter in a fetus with with hydrops fetalis and arthrogryposis multiplex congenita, which died in utero in 3rd trimester.

iii) PMID: 29575618- homozygous c.36122delC (p. P12041Lfs*20) variant in 8 members of a consanguineous family affected with a lethal congenital contracture syndrome and among those 8, three members were IUFD.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 TTN Jasmine Chew gene: TTN was added
gene: TTN was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTN were set to 36977548; 38148006; 29575618
Phenotypes for gene: TTN were set to Lethal congenital contracture syndrome, MONDO:0017436
Review for gene: TTN was set to GREEN
Added comment: i) PMID: 36977548- Reported 10 cases from six unrelated families showing different TTN combinations and four of those cases (F3-iii.1, F6-II.1, F6.ii.3, F6.ii.4) died in utero between 2nd-3rd trimester.
- Quoted that "Probably, we are still missing the most severe end spectrum of titinopathies, as we are used to studying fetuses from late miscarriages or dead infants, while only few investigations are usually performed on early miscarriages. Moreover, prenatal tests often do not include TTN sequencing."

ii)PMID: 38148006- com het p.Arg33743Ter and p.Gln34752Ter in a fetus with with hydrops fetalis and arthrogryposis multiplex congenita, which died in utero in 3rd trimester.

iii) PMID: 29575618- homozygous c.36122delC (p. P12041Lfs*20) variant in 8 members of a consanguineous family affected with a lethal congenital contracture syndrome and among those 8, 3 were IUFD.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 STIL Jasmine Chew changed review comment from: PMID: 29230157- In a family with multiple miscarriages and 2 terminations of pregnancy due to marked fetal microcephaly, delayed cortical gyrification, and dysgenesis of the corpus callosum, compound heterozygous missense variants (p.H411D and p.M124V) identified in two affected male fetuses with partial agenesis of the corpus callosum. Concluded that the compound heterozygous STIL mutations found by WES in the affected fetuses cause the severe neurodevelopmental defects observed by fetal ultrasound and MRI, possibly also causing the recurrent miscarriages for the couple. The 5 miscarriages occurring in the family may suggest a causal relationship between the STIL mutations and embryonic lethality in humans.

ii) PMID: 33772059- A homozygous missense variant p.338H>Y in case 93272, an Iranian family with 4 miscarriages. Fetal autopsy not available for this family. PMID: 10385121 disrupted STIL in mice and the homozygous mutant caused death with neural tube defects, holoprosencephaly and left–right development abnormalities during embryonic development.
Sources: Literature; to: i) PMID: 29230157- In a family with multiple miscarriages and 2 terminations of pregnancy due to marked fetal microcephaly, delayed cortical gyrification, and dysgenesis of the corpus callosum, compound heterozygous missense variants (p.H411D and p.M124V) identified in two affected male fetuses with partial agenesis of the corpus callosum. Functional study showed impairment of the normal regulation of centriole lengthening. Concluded that the compound heterozygous STIL mutations found by WES in the affected fetuses cause the severe neurodevelopmental defects observed by fetal ultrasound and MRI, possibly also causing the recurrent miscarriages for the couple. The 5 miscarriages occurring in the family may suggest a causal relationship between the STIL mutations and embryonic lethality in humans.

ii) PMID: 33772059- A homozygous missense variant p.338H>Y in case 93272, an Iranian family with 4 miscarriages. Fetal autopsy not available for this family. PMID: 10385121 disrupted STIL in mice and the homozygous mutant caused death with neural tube defects, holoprosencephaly and left–right development abnormalities during embryonic development.
Sources: Literature
Prepair 1000+ v1.2068 ROR2 Zornitza Stark Marked gene: ROR2 as ready
Prepair 1000+ v1.2068 ROR2 Zornitza Stark Gene: ror2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2068 ROR2 Zornitza Stark Phenotypes for gene: ROR2 were changed from Robinow syndrome, autosomal recessive, 268310 (3) to Robinow syndrome, autosomal recessive MIM# 268310
Prepair 1000+ v1.2067 ROR2 Zornitza Stark reviewed gene: ROR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Robinow syndrome, autosomal recessive MIM# 268310; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.63 STIL Jasmine Chew changed review comment from: PMID: 29230157- In a family with multiple miscarriages and 2 terminations of pregnancy due to marked fetal microcephaly, delayed cortical gyrification, and dysgenesis of the corpus callosum, compound heterozygous missense variants (p.H411D and p.M124V) identified in two affected male fetuses with partial agenesis of the corpus callosum. Concluded that the compound heterozygous STIL mutations found by WES in the affected fetuses cause the severe neurodevelopmental defects observed by fetal ultrasound and MRI, possibly also causing the recurrent miscarriages for the couple. The 5 miscarriages occurring in the family may suggest a causal relationship between the STIL mutations and embryonic lethality in humans.

ii) PMID: 33772059- A homozygous missense variant p.338H>Y in case 93272, an Iranian family with 4 miscarriages. Fetal autopsy not available for this family. PMID: 10385121 disrupted STIL in mice and the homozygous mutant caused death with neural tube defects, holoprosencephaly and left–right development abnormalities during embryonic development
Sources: Literature; to: PMID: 29230157- In a family with multiple miscarriages and 2 terminations of pregnancy due to marked fetal microcephaly, delayed cortical gyrification, and dysgenesis of the corpus callosum, compound heterozygous missense variants (p.H411D and p.M124V) identified in two affected male fetuses with partial agenesis of the corpus callosum. Concluded that the compound heterozygous STIL mutations found by WES in the affected fetuses cause the severe neurodevelopmental defects observed by fetal ultrasound and MRI, possibly also causing the recurrent miscarriages for the couple. The 5 miscarriages occurring in the family may suggest a causal relationship between the STIL mutations and embryonic lethality in humans.

ii) PMID: 33772059- A homozygous missense variant p.338H>Y in case 93272, an Iranian family with 4 miscarriages. Fetal autopsy not available for this family. PMID: 10385121 disrupted STIL in mice and the homozygous mutant caused death with neural tube defects, holoprosencephaly and left–right development abnormalities during embryonic development.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 STIL Jasmine Chew gene: STIL was added
gene: STIL was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: STIL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STIL were set to 29230157; 33772059
Phenotypes for gene: STIL were set to Recurrent pregnancy loss susceptibility, MONDO:0000144; Primary microcephaly 7, autosomal recessive, MIM# 612703
Review for gene: STIL was set to AMBER
Added comment: PMID: 29230157- In a family with multiple miscarriages and 2 terminations of pregnancy due to marked fetal microcephaly, delayed cortical gyrification, and dysgenesis of the corpus callosum, compound heterozygous missense variants (p.H411D and p.M124V) identified in two affected male fetuses with partial agenesis of the corpus callosum. Concluded that the compound heterozygous STIL mutations found by WES in the affected fetuses cause the severe neurodevelopmental defects observed by fetal ultrasound and MRI, possibly also causing the recurrent miscarriages for the couple. The 5 miscarriages occurring in the family may suggest a causal relationship between the STIL mutations and embryonic lethality in humans.

ii) PMID: 33772059- A homozygous missense variant p.338H>Y in case 93272, an Iranian family with 4 miscarriages. Fetal autopsy not available for this family. PMID: 10385121 disrupted STIL in mice and the homozygous mutant caused death with neural tube defects, holoprosencephaly and left–right development abnormalities during embryonic development
Sources: Literature
Prepair 1000+ v1.2067 RNASET2 Zornitza Stark Marked gene: RNASET2 as ready
Prepair 1000+ v1.2067 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2067 RNASET2 Zornitza Stark Phenotypes for gene: RNASET2 were changed from Leukoencephalopathy, cystic, without megalencephaly, 612951 (3) to Leukoencephalopathy, cystic, without megalencephaly MIM#612951
Prepair 1000+ v1.2066 RNASET2 Zornitza Stark Publications for gene: RNASET2 were set to
Prepair 1000+ v1.2065 RNASEH2A Zornitza Stark Marked gene: RNASEH2A as ready
Prepair 1000+ v1.2065 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Prepair 1000+ v1.2065 RNASEH2A Zornitza Stark Phenotypes for gene: RNASEH2A were changed from Aicardi-Goutieres syndrome 4, 610333 (3) to Aicardi-Goutieres syndrome 4 MIM#610333; RNASEH2A-related type 1 interferonopathy MONDO:0700259
Prepair 1000+ v1.2064 RNASEH2A Zornitza Stark Publications for gene: RNASEH2A were set to
Prepair 1000+ v1.2063 RFX6 Zornitza Stark Marked gene: RFX6 as ready
Prepair 1000+ v1.2063 RFX6 Zornitza Stark Gene: rfx6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2063 RFX6 Zornitza Stark Phenotypes for gene: RFX6 were changed from Mitchell-Riley syndrome, 615710 (3) to Mitchell-Riley syndrome, MIM# 615710
Prepair 1000+ v1.2062 RFX6 Zornitza Stark reviewed gene: RFX6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitchell-Riley syndrome, MIM# 615710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2062 RFT1 Zornitza Stark Marked gene: RFT1 as ready
Prepair 1000+ v1.2062 RFT1 Zornitza Stark Gene: rft1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2062 RFT1 Zornitza Stark Phenotypes for gene: RFT1 were changed from Congenital disorder of glycosylation, type In, 612015 (3) to Congenital disorder of glycosylation, type In, MIM# 612015
Prepair 1000+ v1.2061 RFT1 Zornitza Stark Publications for gene: RFT1 were set to
Prepair 1000+ v1.2060 RFT1 Zornitza Stark reviewed gene: RFT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18313027, 19701946, 19856127, 23111317, 30071302, 29923091, 27927990, 26892341; Phenotypes: Congenital disorder of glycosylation, type In, MIM# 612015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2060 RD3 Zornitza Stark Marked gene: RD3 as ready
Prepair 1000+ v1.2060 RD3 Zornitza Stark Gene: rd3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2060 RD3 Zornitza Stark reviewed gene: RD3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber congenital amaurosis 12, MIM#610612; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2060 RARB Zornitza Stark Tag for review tag was added to gene: RARB.
Prepair 1000+ v1.2060 RAG1 Zornitza Stark Marked gene: RAG1 as ready
Prepair 1000+ v1.2060 RAG1 Zornitza Stark Gene: rag1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2060 RAG1 Zornitza Stark Phenotypes for gene: RAG1 were changed from Severe combined immunodeficiency, B cell-negative, 601457 (3) to Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889; Combined cellular and humoral immune defects with granulomas MIM# 233650; Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457
Prepair 1000+ v1.2059 RAG1 Zornitza Stark reviewed gene: RAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889, Combined cellular and humoral immune defects with granulomas MIM# 233650, Omenn syndrome MIM# 603554, Severe combined immunodeficiency, B cell-negative MIM# 601457; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.63 TIMP2 Jasmine Chew gene: TIMP2 was added
gene: TIMP2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: TIMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TIMP2 were set to 20847186; 34756330
Phenotypes for gene: TIMP2 were set to Recurrent pregnancy loss susceptibility, MONDO:0000144
Review for gene: TIMP2 was set to AMBER
Added comment: i) PMID: 20847186- In family 6, TIMP2 partial duplication (involves Ex1-2) in mother and 4 out of 5 miscarriages. They have not yet been associated with RPL in humans, however, overexpression of TIMP2 was detected in a mouse model of RPL (Dixon et al., 2006). The TIMP2 disruption in miscarriages in Family 6 may have affected the placental development, but the possibility remains that maternal disruption of TIMP2 may contribute to RPL by impairing the remodeling of the endometrium in early pregnancy. Functional study was performed by PMID: 25674159, which showed reduced RNA and protein expression in chorionic villi cultures from miscarriages with the CNV.

ii) PMID: 34756330- de novo damaging heterozygous missense TIMP2 variant, c.[553G>A]; p.[Gly185Arg] in an eight-week euploid embryonic loss. The MMP2/TIMP2 complex is involved in several gestational processes including implantation and placentation.

iii) PMID: 11912288- The disruption of the TIMP2 gene was considered to be relevant for recurrent miscarriage due to its critical role in modulating invasion of the trophoblast into maternal endometrium and in vascular remodeling and angiogenesis of maternal and placenta tissues in the first trimester.
Sources: Literature
Prepair 1000+ v1.2059 PYCR1 Zornitza Stark Marked gene: PYCR1 as ready
Prepair 1000+ v1.2059 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2059 PYCR1 Zornitza Stark Phenotypes for gene: PYCR1 were changed from Cutis laxa, autosomal recessive, type IIB, 612940 (3) to Cutis laxa, autosomal recessive, type IIB MIM#612940; Cutis laxa, autosomal recessive, type IIIB MIM#614438
Prepair 1000+ v1.2058 PYCR1 Zornitza Stark reviewed gene: PYCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cutis laxa, autosomal recessive, type IIB MIM#612940, Cutis laxa, autosomal recessive, type IIIB MIM#614438; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2058 PSMB8 Zornitza Stark Marked gene: PSMB8 as ready
Prepair 1000+ v1.2058 PSMB8 Zornitza Stark Gene: psmb8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2058 PSMB8 Zornitza Stark Phenotypes for gene: PSMB8 were changed from Autoinflammation, lipodystrophy, and dermatosis syndrome, 256040 (3) to Proteasome-associated autoinflammatory syndrome 1, MIM# 256040; MONDO:0054698
Prepair 1000+ v1.2057 PSMB8 Zornitza Stark Publications for gene: PSMB8 were set to
Prepair 1000+ v1.2056 PSMB8 Zornitza Stark reviewed gene: PSMB8: Rating: GREEN; Mode of pathogenicity: None; Publications: 21129723, 21881205, 21852578, 21953331; Phenotypes: Proteasome-associated autoinflammatory syndrome 1, MIM# 256040, MONDO:0054698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2056 PROS1 Zornitza Stark Marked gene: PROS1 as ready
Prepair 1000+ v1.2056 PROS1 Zornitza Stark Gene: pros1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2056 PROS1 Zornitza Stark Phenotypes for gene: PROS1 were changed from Thrombophilia due to protein S deficiency, autosomal recessive, 614514 (3) to Thrombophilia 5 due to protein S deficiency, autosomal recessive #614514
Prepair 1000+ v1.2055 PROS1 Zornitza Stark reviewed gene: PROS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombophilia 5 due to protein S deficiency, autosomal recessive #614514; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2055 PPIB Zornitza Stark Marked gene: PPIB as ready
Prepair 1000+ v1.2055 PPIB Zornitza Stark Gene: ppib has been classified as Green List (High Evidence).
Prepair 1000+ v1.2055 PPIB Zornitza Stark Phenotypes for gene: PPIB were changed from Osteogenesis imperfecta, type IX, #259440 to Osteogenesis imperfecta, type IX MIM#259440
Prepair 1000+ v1.2054 PPIB Zornitza Stark Publications for gene: PPIB were set to
Prepair 1000+ v1.2053 POMT2 Zornitza Stark Marked gene: POMT2 as ready
Prepair 1000+ v1.2053 POMT2 Zornitza Stark Gene: pomt2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2053 POMT2 Zornitza Stark Phenotypes for gene: POMT2 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2, 613150 (3) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2, MIM# 613150; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 2, MIM# 613156
Prepair 1000+ v1.2052 POMT2 Zornitza Stark Publications for gene: POMT2 were set to
Prepair 1000+ v1.2051 POLG Zornitza Stark Marked gene: POLG as ready
Prepair 1000+ v1.2051 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Prepair 1000+ v1.2051 POLG Zornitza Stark Phenotypes for gene: POLG were changed from Mitochondrial DNA depletion syndrome 4A (Alpers type), 203700 (3) to Mitochondrial DNA depletion syndrome 4A (Alpers type), MIM# 203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type), MIM#613662
Prepair 1000+ v1.2050 POLG Zornitza Stark reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 4A (Alpers type), MIM# 203700, Mitochondrial DNA depletion syndrome 4B (MNGIE type), MIM#613662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.63 KIF14 Jasmine Chew edited their review of gene: KIF14: Changed phenotypes: Autosomal recessive lethal fetal ciliopathy
Infertility and Recurrent Pregnancy Loss v0.63 KIF14 Jasmine Chew gene: KIF14 was added
gene: KIF14 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: KIF14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF14 were set to 24128419; 30388224
Review for gene: KIF14 was set to GREEN
Added comment: i) PMID: 24128419- First human phenotype associated with biallelic inactivating mutations of KIF14, reported 2 affected fetuses in a family with a recurrent fetal pattern of multiple congenital anomalies (MCA), which was considered to be lethal because of distinct brain and kidney malformations, which were both terminated before 20 weeks carrying LOF com het p.Glu584Ilefs*16 and p.Arg594*.Very recently, homozygous mutations in Kif14 (G/A substitution at the 3′ splice acceptor site of Kif14 exon 5) were identified in a novel spontaneous mouse mutant, laggard (lag). which recapitulated most of the fetal phenotypes including the brain malformations, reduced brain size, general growth restriction and early lethality seen in this family (PMID: 23308235).

ii) PMID: 30388224- Novel biallelic KIF14 variants in fetuses (IUFD) from 4 unrelated families presenting with strikingly similar severe brain and kidney phenotypes- renal hypodysplasia and microcephaly, diagnosed as lethal, highly penetrant syndromic CAKUT with microcephaly. Functional studies using transfection study and zebrafish models are supportive that loss of KIF14 result in defects in cytokinesis, microcephaly and ciliopathy-related phenotypes.
Sources: Literature
Prepair 1000+ v1.2050 PNPLA6 Zornitza Stark Marked gene: PNPLA6 as ready
Prepair 1000+ v1.2050 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2050 PNPLA6 Zornitza Stark Phenotypes for gene: PNPLA6 were changed from Boucher-Neuhauser syndrome, 215470 (3) to Boucher-Neuhauser syndrome MIM#215470; Oliver-McFarlane syndrome MIM#275400; Spastic paraplegia 39, autosomal recessive MIM#612020
Prepair 1000+ v1.2049 PNPLA6 Zornitza Stark Publications for gene: PNPLA6 were set to
Prepair 1000+ v1.2048 PNP Zornitza Stark Marked gene: PNP as ready
Prepair 1000+ v1.2048 PNP Zornitza Stark Gene: pnp has been classified as Green List (High Evidence).
Prepair 1000+ v1.2048 PNP Zornitza Stark Publications for gene: PNP were set to
Prepair 1000+ v1.2047 PNP Zornitza Stark edited their review of gene: PNP: Changed publications: 3029074, 1384322, 11453975, 32695102, 32514656
Prepair 1000+ v1.2047 PNP Zornitza Stark Phenotypes for gene: PNP were changed from Immunodeficiency due to purine nucleoside phosphorylase deficiency, 613179 (3) to Immunodeficiency due to purine nucleoside phosphorylase deficiency, MIM# 613179
Prepair 1000+ v1.2046 PNP Zornitza Stark reviewed gene: PNP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency due to purine nucleoside phosphorylase deficiency, MIM# 613179; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2046 PHF6 Zornitza Stark Marked gene: PHF6 as ready
Prepair 1000+ v1.2046 PHF6 Zornitza Stark Gene: phf6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2046 PHF6 Zornitza Stark Phenotypes for gene: PHF6 were changed from Borjeson-Forssman-Lehmann syndrome, 301900 (3) to Borjeson-Forssman-Lehmann syndrome, MIM# 301900
Prepair 1000+ v1.2045 PHF6 Zornitza Stark reviewed gene: PHF6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Borjeson-Forssman-Lehmann syndrome, MIM# 301900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Infertility and Recurrent Pregnancy Loss v0.63 GBE1 Jasmine Chew gene: GBE1 was added
gene: GBE1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: GBE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBE1 were set to 33772059; 25489661; 26166723
Phenotypes for gene: GBE1 were set to Glycogen storage disease IV, MIM# 232500
Review for gene: GBE1 was set to GREEN
Added comment: i) PMID: 33772059- one Iranian family with RPL (Fam 90759 , a 13-week fetus with hydrops fetalis observed in ultrasonography) carrying compound heterozygous p.156R>H and c.-35_-54del GCTCAGGCCCCACTCGACCC.

ii) PMID: 25489661- compound heterozygous c.1937delT and c.691+2T>C in a female with spontaneous miscarriage at 8 weeks of gestation with diagnosis of Glycogen storage disease type IV (GSD IV) supported by pathological examination of immature villi.

iii) PMID: 26166723-ompound heterozygous c.691+2T>C and p.R524X in A 30-yr-old woman presented with 2 consecutive miscarriages within 7 month with diagnosis of Glycogen storage disease type IV (GSD IV) supported by pathological examination of placental tissues. Concluded that glycogen storage disease Type IV can cause early miscarriage and that diagnosis can initially be made on histopathologic examination.
Sources: Literature
Prepair 1000+ v1.2045 PET100 Zornitza Stark Marked gene: PET100 as ready
Prepair 1000+ v1.2045 PET100 Zornitza Stark Gene: pet100 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2045 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from Mitochondrial complex IV deficiency, 220110 (3) to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Prepair 1000+ v1.2044 PET100 Zornitza Stark reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2044 PDP1 Zornitza Stark Marked gene: PDP1 as ready
Prepair 1000+ v1.2044 PDP1 Zornitza Stark Gene: pdp1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2044 PDP1 Zornitza Stark Phenotypes for gene: PDP1 were changed from Pyruvate dehydrogenase phosphatase deficiency, 608782 (3) to Pyruvate dehydrogenase phosphatase deficiency,MIM#608782
Prepair 1000+ v1.2043 PDP1 Zornitza Stark Publications for gene: PDP1 were set to
Prepair 1000+ v1.2042 PCSK1 Zornitza Stark Marked gene: PCSK1 as ready
Prepair 1000+ v1.2042 PCSK1 Zornitza Stark Gene: pcsk1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2042 PCSK1 Zornitza Stark Phenotypes for gene: PCSK1 were changed from Obesity with impaired prohormone processing, 600955 (3) to Endocrinopathy due to proprotein convertase 1/3 deficiency,MIM#600955
Infertility and Recurrent Pregnancy Loss v0.63 SCN5A Jasmine Chew gene: SCN5A was added
gene: SCN5A was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: SCN5A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SCN5A were set to 33772059; 32421437; 23571586; 15184283
Review for gene: SCN5A was set to GREEN
Added comment: i) PMID: 33772059- An Iranian family with RPL (Fam 94947) without fetal autopsy carrying homozygous missense p.1250T>M. The parents were both carriers with a history of cardiac events in the family. This variant has been reported to cause long QT syndrome 3 (LQT3) (#603830) in the heterozygous state. Homozygous mutations in SCN5A in mice cause intrauterine lethality mostly during organogenesis due to heart defects (PMID: 11972032).

ii) PMID: 32421437- de novo SCN5A variants in four cases which all died and three of them died in utero.

iii) PMID: 23571586- 5 intrauterine fetal deaths hosted SCN5A rare nonsynonymous genetic variants (p.T220I, p.R1193Q, involving 2 cases, and p.P2006A, involving 2 cases).

iv) PMID: 15184283- A case of recurrent third-trimester fetal loss and maternal mosaicism for long-QT syndrome- low level mosaic R1623Q present in mom and cord blood from the third fetus also harbored the mutant allele, suggesting that all 3 cases of late-term fetal distress resulted from germ-line transfer of the LQTS-associated mutation.
Sources: Literature
Prepair 1000+ v1.2041 PCSK1 Zornitza Stark Publications for gene: PCSK1 were set to
Prepair 1000+ v1.2040 PCCA Zornitza Stark Marked gene: PCCA as ready
Prepair 1000+ v1.2040 PCCA Zornitza Stark Gene: pcca has been classified as Green List (High Evidence).
Prepair 1000+ v1.2040 PCCA Zornitza Stark Phenotypes for gene: PCCA were changed from Propionicacidemia, 606054 (3) to Propionicacidemia, MIM#606054
Prepair 1000+ v1.2039 PCCA Zornitza Stark Publications for gene: PCCA were set to
Prepair 1000+ v1.2038 PAK3 Zornitza Stark Marked gene: PAK3 as ready
Prepair 1000+ v1.2038 PAK3 Zornitza Stark Gene: pak3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2038 PAK3 Zornitza Stark Phenotypes for gene: PAK3 were changed from Mental retardation, X-linked 30/47, 300558 (3) to Intellectual developmental disorder, X-linked 30 MIM#300558
Prepair 1000+ v1.2037 PAK3 Zornitza Stark Publications for gene: PAK3 were set to
Infertility and Recurrent Pregnancy Loss v0.63 FRAS1 Jasmine Chew changed review comment from: New papers:
i) PMID: 33772059- An Iranian family with RPL (Fam 90377 with fetal autopsy showing 17 weeks male with Fraser syndrome and Bartsocas-Papas syndrome- syndactyly, dysplastic ears, right kidney agenesis, club foot, flexion contracture of the hip, and atretic external auditory canals) carrying a homozygous missense variant, p.135T>M.

ii) PMID: 32643034- Four affected fetus from 4 independent families carrying novel homozygous LOF variants (p.His2995Profs*3, c.9780+2T>C, c.8098+2T>A, c.5217+1G>C) All these affected families had history of miscarriages/ intrauterine fetal loss.
Sources: Literature; to: New papers:
i) PMID: 33772059- An Iranian family with RPL (Fam 90377 with fetal autopsy showing 17 weeks male with Fraser syndrome and Bartsocas-Papas syndrome- syndactyly, dysplastic ears, right kidney agenesis, club foot, flexion contracture of the hip, and atretic external auditory canals) carrying a homozygous missense variant, p.135T>M.

ii) PMID: 32643034- Four affected fetus from 4 independent families carrying novel homozygous LOF variants (p.His2995Profs*3, c.9780+2T>C, c.8098+2T>A, c.5217+1G>C) All these affected families had history of miscarriages/ intrauterine fetal loss due to oligohydramnios, renal agenesis and other congenital anomalies.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 FRAS1 Jasmine Chew gene: FRAS1 was added
gene: FRAS1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: FRAS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRAS1 were set to 33772059; 32643034
Phenotypes for gene: FRAS1 were set to Fraser syndrome 1, MIM# 219000
Review for gene: FRAS1 was set to GREEN
Added comment: New papers:
i) PMID: 33772059- An Iranian family with RPL (Fam 90377 with fetal autopsy showing 17 weeks male with Fraser syndrome and Bartsocas-Papas syndrome- syndactyly, dysplastic ears, right kidney agenesis, club foot, flexion contracture of the hip, and atretic external auditory canals) carrying a homozygous missense variant, p.135T>M.

ii) PMID: 32643034- Four affected fetus from 4 independent families carrying novel homozygous LOF variants (p.His2995Profs*3, c.9780+2T>C, c.8098+2T>A, c.5217+1G>C) All these affected families had history of miscarriages/ intrauterine fetal loss.
Sources: Literature
Prepair 1000+ v1.2036 PAH Zornitza Stark Marked gene: PAH as ready
Prepair 1000+ v1.2036 PAH Zornitza Stark Gene: pah has been classified as Green List (High Evidence).
Prepair 1000+ v1.2036 PAH Zornitza Stark Phenotypes for gene: PAH were changed from Phenylketonuria, 261600 (3) to Phenylketonuria, MIM#261600
Prepair 1000+ v1.2035 PAH Zornitza Stark Publications for gene: PAH were set to
Prepair 1000+ v1.2034 OTUD6B Zornitza Stark Marked gene: OTUD6B as ready
Prepair 1000+ v1.2034 OTUD6B Zornitza Stark Gene: otud6b has been classified as Green List (High Evidence).
Prepair 1000+ v1.2034 OTUD6B Zornitza Stark Phenotypes for gene: OTUD6B were changed from Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 617452 (3), Autosomal recessive to Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies,MIM#617452
Prepair 1000+ v1.2033 OTUD6B Zornitza Stark Publications for gene: OTUD6B were set to
Prepair 1000+ v1.2032 LRSAM1 Lilian Downie Marked gene: LRSAM1 as ready
Prepair 1000+ v1.2032 LRSAM1 Lilian Downie Added comment: Comment when marking as ready: Only single AR family reported, insufficient evidence, downgrade to RED
Prepair 1000+ v1.2032 LRSAM1 Lilian Downie Gene: lrsam1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2032 LRSAM1 Lilian Downie Publications for gene: LRSAM1 were set to
Prepair 1000+ v1.2031 OSGEP Zornitza Stark Marked gene: OSGEP as ready
Prepair 1000+ v1.2031 OSGEP Zornitza Stark Gene: osgep has been classified as Green List (High Evidence).
Prepair 1000+ v1.2031 OSGEP Zornitza Stark Phenotypes for gene: OSGEP were changed from Galloway-Mowat syndrome 3, 617729 (3), Autosomal recessive to Galloway-Mowat syndrome 3, MIM# 617729
Prepair 1000+ v1.2030 OSGEP Zornitza Stark Publications for gene: OSGEP were set to
Prepair 1000+ v1.2029 OSGEP Zornitza Stark reviewed gene: OSGEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828, 28272532; Phenotypes: Galloway-Mowat syndrome 3, MIM# 617729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.2029 OPA1 Zornitza Stark Marked gene: OPA1 as ready
Prepair 1000+ v1.2029 OPA1 Zornitza Stark Gene: opa1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2029 OPA1 Zornitza Stark Phenotypes for gene: OPA1 were changed from Behr syndrome, 210000 (3), Autosomal recessive to Behr syndrome, MIM#210000
Prepair 1000+ v1.2028 OPA1 Zornitza Stark Publications for gene: OPA1 were set to
Prepair 1000+ v1.2027 PUS7 Lilian Downie Marked gene: PUS7 as ready
Prepair 1000+ v1.2027 PUS7 Lilian Downie Added comment: Comment when marking as ready: Upgrade to green
Prepair 1000+ v1.2027 PUS7 Lilian Downie Gene: pus7 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2027 NUP107 Zornitza Stark Marked gene: NUP107 as ready
Prepair 1000+ v1.2027 NUP107 Zornitza Stark Gene: nup107 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2027 NUP107 Zornitza Stark Phenotypes for gene: NUP107 were changed from Nephrotic syndrome, type 11, 616730 (3), Autosomal recessive to Galloway-Mowat syndrome 7, MIM#618348; Nephrotic syndrome, type 11, MIM#616730
Prepair 1000+ v1.2026 NUP107 Zornitza Stark Publications for gene: NUP107 were set to
Prepair 1000+ v1.2025 NUBPL Zornitza Stark Marked gene: NUBPL as ready
Prepair 1000+ v1.2025 NUBPL Zornitza Stark Gene: nubpl has been classified as Green List (High Evidence).
Prepair 1000+ v1.2025 NUBPL Zornitza Stark Phenotypes for gene: NUBPL were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 21, MIM#618242
Prepair 1000+ v1.2024 NUBPL Zornitza Stark Publications for gene: NUBPL were set to
Prepair 1000+ v1.2023 NR0B1 Zornitza Stark Marked gene: NR0B1 as ready
Prepair 1000+ v1.2023 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2023 NR0B1 Zornitza Stark Phenotypes for gene: NR0B1 were changed from 46XY sex reversal 2, dosage-sensitive, 300018 (3) to Adrenal hypoplasia, congenital, MIM#300200
Prepair 1000+ v1.2022 NR0B1 Zornitza Stark Publications for gene: NR0B1 were set to
Prepair 1000+ v1.2021 NDUFV2 Zornitza Stark Marked gene: NDUFV2 as ready
Prepair 1000+ v1.2021 NDUFV2 Zornitza Stark Gene: ndufv2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2021 NDUFV2 Zornitza Stark Phenotypes for gene: NDUFV2 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 7, MIM#618229, MONDO:0044970
Prepair 1000+ v1.2020 NDUFV2 Zornitza Stark Publications for gene: NDUFV2 were set to
Prepair 1000+ v1.2019 NDUFS4 Zornitza Stark Marked gene: NDUFS4 as ready
Prepair 1000+ v1.2019 NDUFS4 Zornitza Stark Gene: ndufs4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2019 NDUFS4 Zornitza Stark Phenotypes for gene: NDUFS4 were changed from Leigh syndrome, 256000 (3) to Mitochondrial complex I deficiency, nuclear type 1, MIM#252010
Prepair 1000+ v1.2018 NCF1 Lilian Downie Tag for review tag was added to gene: NCF1.
Prepair 1000+ v1.2018 NDP Zornitza Stark Marked gene: NDP as ready
Prepair 1000+ v1.2018 NDP Zornitza Stark Gene: ndp has been classified as Green List (High Evidence).
Prepair 1000+ v1.2018 NDP Zornitza Stark Phenotypes for gene: NDP were changed from Norrie disease, 310600 (3) to Norrie disease, MIM#310600
Prepair 1000+ v1.2017 NDP Zornitza Stark Publications for gene: NDP were set to
Prepair 1000+ v1.2016 NDE1 Zornitza Stark Marked gene: NDE1 as ready
Prepair 1000+ v1.2016 NDE1 Zornitza Stark Gene: nde1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2016 NDE1 Zornitza Stark Phenotypes for gene: NDE1 were changed from Lissencephaly 4 (with microcephaly), 614019 (3) to Lissencephaly 4 (with microcephaly), MIM#614019
Prepair 1000+ v1.2015 NDE1 Zornitza Stark Publications for gene: NDE1 were set to
Prepair 1000+ v1.2014 NCF2 Zornitza Stark Marked gene: NCF2 as ready
Prepair 1000+ v1.2014 NCF2 Zornitza Stark Gene: ncf2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2014 NCF2 Zornitza Stark Phenotypes for gene: NCF2 were changed from Chronic granulomatous disease due to deficiency of NCF-2, 233710 (3) to Chronic granulomatous disease 2, autosomal recessive, MIM# 233710
Prepair 1000+ v1.2013 NCF2 Zornitza Stark Publications for gene: NCF2 were set to
Prepair 1000+ v1.2012 NAGA Zornitza Stark Marked gene: NAGA as ready
Prepair 1000+ v1.2012 NAGA Zornitza Stark Gene: naga has been classified as Green List (High Evidence).
Prepair 1000+ v1.2012 NAGA Zornitza Stark Phenotypes for gene: NAGA were changed from Schindler disease, type I, 609241 (3) to Schindler disease, type I MIM#609241; Schindler disease, type III MIM#609241
Prepair 1000+ v1.2011 NAGA Zornitza Stark Publications for gene: NAGA were set to
Prepair 1000+ v1.2010 PDE6B Lilian Downie Marked gene: PDE6B as ready
Prepair 1000+ v1.2010 PDE6B Lilian Downie Gene: pde6b has been classified as Red List (Low Evidence).
Prepair 1000+ v1.2010 MYD88 Zornitza Stark Marked gene: MYD88 as ready
Prepair 1000+ v1.2010 MYD88 Zornitza Stark Gene: myd88 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2010 PDE6B Lilian Downie Publications for gene: PDE6B were set to
Prepair 1000+ v1.2009 MYD88 Zornitza Stark Phenotypes for gene: MYD88 were changed from Pyogenic bacterial infections, recurrent, due to MYD88 deficiency, 612260 (3) to Immunodeficiency 68, MIM# 612260
Prepair 1000+ v1.2008 MYD88 Zornitza Stark Publications for gene: MYD88 were set to
Prepair 1000+ v1.2007 MUSK Zornitza Stark Marked gene: MUSK as ready
Prepair 1000+ v1.2007 MUSK Zornitza Stark Gene: musk has been classified as Green List (High Evidence).
Prepair 1000+ v1.2007 MUSK Zornitza Stark Phenotypes for gene: MUSK were changed from Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, 616325 (3) to Fetal akinesia deformation sequence 1 MIM#208150; Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency MIM#616325
Prepair 1000+ v1.2006 MUSK Zornitza Stark Publications for gene: MUSK were set to
Prepair 1000+ v1.2005 GBA Lilian Downie Marked gene: GBA as ready
Prepair 1000+ v1.2005 GBA Lilian Downie Added comment: Comment when marking as ready: Consider upgrading to green as most common variant detectable and suitable disease for inclusion.
Prepair 1000+ v1.2005 GBA Lilian Downie Gene: gba has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.63 PIEZO1 Jasmine Chew gene: PIEZO1 was added
gene: PIEZO1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: PIEZO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIEZO1 were set to 33772059; 30244526; 26333996
Phenotypes for gene: PIEZO1 were set to Lymphatic malformation 6, MIM# 616843
Review for gene: PIEZO1 was set to GREEN
Added comment: i) PMID: 33772059- Two unrelated Iranian families with RPL carrying different biallelic variants (i. Fam 82169 with fetal autopsy showing generalized lymphatic dysplasia of Fotiou with non-immune fetal hydrops carry homozygous LOF c.30_31delAC, ii) fam 95136 without fetal autopsy carrying compound heterozygous p.2195S>L and p.922G>W).

ii) PMID: 30244526- Compound heterozygous variants p.Trp1069* and p.Lys2070Gln in a case of a woman with recurrent pregnancies affected by NIHF and had three fetal demises because of severe lymphatic dysplasia.

iii) PMID: 26333996- In a recent review of 10 patients within 6 families, 7 of the probands were diagnosed with NIHF, including 2 died in utero, carrying biallelic variants.
Sources: Literature
Prepair 1000+ v1.2005 CHMP1A Lilian Downie Marked gene: CHMP1A as ready
Prepair 1000+ v1.2005 CHMP1A Lilian Downie Added comment: Comment when marking as ready: Inclusion, green on PanelApp and severe childhood disease
Prepair 1000+ v1.2005 CHMP1A Lilian Downie Gene: chmp1a has been removed from the panel.
Infertility and Recurrent Pregnancy Loss v0.63 BTG4 Jasmine Chew gene: BTG4 was added
gene: BTG4 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: BTG4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BTG4 were set to 32502391; 34647228
Phenotypes for gene: BTG4 were set to Oocyte/zygote/embryo maturation arrest 8, MIM# 619009
Review for gene: BTG4 was set to GREEN
Added comment: Literature in OMIM- PMID: 32502391, 34647228- >3 unrelated infertile women due to failure of the fertilized ovum to undergo zygotic cleavage with different biallelic variants. Functional analysis demonstrated LOF, such as reduced mutant protein expression and disruption in the process of maternal mRNA decay, and loss of protein-protein interaction.

New paper:
i) PMID: 36471203- A novel homozygous truncating variant (p.V195Sfs) in a a female patient with primary infertility and recurrent failure of IVF with zygotic cleavage failure. Co-immunoprecipitation in 293 T cells showed that the mutation abolished the interaction between BTG4 and PABPN1L.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 NLRP2 Jasmine Chew gene: NLRP2 was added
gene: NLRP2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: NLRP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NLRP2 were set to 30877238; 39585517; 39905760
Phenotypes for gene: NLRP2 were set to Oocyte/zygote/embryo maturation arrest 18, MIM# 620332
Review for gene: NLRP2 was set to GREEN
Added comment: Literature in OMIM- PMID: 30877238 (>3 unrelated infertile women due to early embryonic arrest with different biallelic variants)

New papers (biallelic variants for EEA):
i) PMID: 39585517- A novel homozygous protein-truncating (p.Tyr66Thrfs*32) in an infertile female with early embryonic arrest, which resulted in the down-regulation of NLRP2 mRNA expression, truncation of the protein structure, and altered protein localization in cells.

ii) PMID: 39905760- Novel compound heterozygous protein-truncating variants ( p.Leu443Phefs*78 and p.Arg935Metfs*15) in a female with primary infertility, four early miscarriages, and one failed attempt of ICSI. The two variants mediate mRNA decay in EBV-transformed lymphoblastoid cells from the patient, lead to decreased NLRP2 protein levels, and alter NLRP2 interactions with other members of the SCMC in vitro.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 MOS Jasmine Chew gene: MOS was added
gene: MOS was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: MOS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOS were set to 34779126; 34997960; 35670744; 36403623
Phenotypes for gene: MOS were set to Oocyte/zygote/embryo maturation arrest 20, MIM# 620383
Review for gene: MOS was set to GREEN
Added comment: Literature in OMIM- PMID: 34779126; 34997960; 35670744; 36403623- >3 unrelated women with infertility due to early/preimplantation embryonic arrest and fragmentation carrying different biallelic variants. All variants except I197M had functional evidence showing that mutant proteins showed reduced activation/phosphorylation of the MOS downstream targets compared to wildtype MOS.
Note: couldn't find new case reports
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 KPNA7 Jasmine Chew gene: KPNA7 was added
gene: KPNA7 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: KPNA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KPNA7 were set to 36647821
Phenotypes for gene: KPNA7 were set to Oocyte/zygote/embryo maturation arrest 17, #MIM 620319
Review for gene: KPNA7 was set to GREEN
Added comment: Literature in OMIM- PMID:36647821- 10 Chinese women from 10 independent families with infertility due to preimplantation embryo arrest carrying the following biallelic variants: x6 homozygous L203F missense, x3 compound heterozygous L203F/P212L, L203F/Q175K, L203F/C451X, and x1 homozygous V152M. Western blot of transfected HEK293T cells showed that all mutant protein levels were significantly lower than wildtype KPNA7. Mutant KPNA7 showed significantly reduced SV40TNLS protein transport activity compared to wildtype KPNA7.
- There were no homozygotes for the recurrent L203F variant either in public databases or in-house control databases. Homozygosity mapping analysis suggested a low probability of founder effect for the recurrent variant L203F.

Note: couldn't find new case reports
Sources: Literature
Prepair 1000+ v1.2005 MTTP Zornitza Stark Marked gene: MTTP as ready
Prepair 1000+ v1.2005 MTTP Zornitza Stark Gene: mttp has been classified as Green List (High Evidence).
Prepair 1000+ v1.2005 MTTP Zornitza Stark Phenotypes for gene: MTTP were changed from Abetalipoproteinemia, 200100 (3) to Abetalipoproteinemia MIM#200100
Prepair 1000+ v1.2004 MTTP Zornitza Stark Publications for gene: MTTP were set to
Prepair 1000+ v1.2003 MTHFD1 Zornitza Stark Marked gene: MTHFD1 as ready
Prepair 1000+ v1.2003 MTHFD1 Zornitza Stark Gene: mthfd1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2003 MTHFD1 Zornitza Stark Phenotypes for gene: MTHFD1 were changed from Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia, 617780 (3), Autosomal recessive to Combined immunodeficiency and megaloblastic anaemia with or without hyperhomocysteinemia, 617780 (3), Autosomal recessive
Prepair 1000+ v1.2002 MTHFD1 Zornitza Stark Publications for gene: MTHFD1 were set to
Prepair 1000+ v1.2001 MSTO1 Zornitza Stark Marked gene: MSTO1 as ready
Prepair 1000+ v1.2001 MSTO1 Zornitza Stark Gene: msto1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2001 MSTO1 Zornitza Stark Publications for gene: MSTO1 were set to 30684668; 31463572
Prepair 1000+ v1.2000 MMP2 Zornitza Stark Marked gene: MMP2 as ready
Prepair 1000+ v1.2000 MMP2 Zornitza Stark Gene: mmp2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.2000 MMP2 Zornitza Stark Phenotypes for gene: MMP2 were changed from Multicentric osteolysis, nodulosis, and arthropathy, 259600 (3) to Multicentric osteolysis, nodulosis, and arthropathy, MIM#259600
Prepair 1000+ v1.1999 MMP2 Zornitza Stark Publications for gene: MMP2 were set to
Prepair 1000+ v1.1998 MLC1 Zornitza Stark Marked gene: MLC1 as ready
Prepair 1000+ v1.1998 MLC1 Zornitza Stark Gene: mlc1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1998 MLC1 Zornitza Stark Phenotypes for gene: MLC1 were changed from Megalencephalic leukoencephalopathy with subcortical cysts, 604004 (3) to Megalencephalic leukoencephalopathy with subcortical cysts 1, MIM #604004
Prepair 1000+ v1.1997 MLC1 Zornitza Stark Publications for gene: MLC1 were set to
Prepair 1000+ v1.1996 MKS1 Zornitza Stark Marked gene: MKS1 as ready
Prepair 1000+ v1.1996 MKS1 Zornitza Stark Gene: mks1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1996 MKS1 Zornitza Stark Phenotypes for gene: MKS1 were changed from Meckel syndrome 1, 249000 (3) to Bardet-Biedl syndrome 13 MIM#615990; Joubert syndrome 28 MIM#617121; Meckel syndrome 1 MIM#249000; Ciliopathy MONDO:0005308
Prepair 1000+ v1.1995 MKS1 Zornitza Stark Publications for gene: MKS1 were set to
Prepair 1000+ v1.1994 MICU1 Zornitza Stark Marked gene: MICU1 as ready
Prepair 1000+ v1.1994 MICU1 Zornitza Stark Gene: micu1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1994 MICU1 Zornitza Stark Phenotypes for gene: MICU1 were changed from Myopathy with extrapyramidal signs, 615673 (3) to Myopathy with extrapyramidal signs, MIM# 615673
Prepair 1000+ v1.1993 MICU1 Zornitza Stark Publications for gene: MICU1 were set to
Prepair 1000+ v1.1992 MFN2 Zornitza Stark Marked gene: MFN2 as ready
Prepair 1000+ v1.1992 MFN2 Zornitza Stark Gene: mfn2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1992 MFN2 Zornitza Stark Phenotypes for gene: MFN2 were changed from Charcot-Marie-Tooth disease, axonal, type 2A2B, 617087 (3), Autosomal recessive to Charcot-Marie-Tooth disease, axonal, type 2A2B, MIM# 617087; Lipomatosis, multiple symmetric, with or without peripheral neuropathy, MIM# 151800
Prepair 1000+ v1.1991 MFN2 Zornitza Stark reviewed gene: MFN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lipomatosis, multiple symmetric, with or without peripheral neuropathy, MIM# 151800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1991 MFN2 Zornitza Stark Publications for gene: MFN2 were set to
Prepair 1000+ v1.1990 METTL23 Zornitza Stark Marked gene: METTL23 as ready
Prepair 1000+ v1.1990 METTL23 Zornitza Stark Gene: mettl23 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1990 METTL23 Zornitza Stark Phenotypes for gene: METTL23 were changed from Mental retardation, autosomal recessive 44, 615942 (3) to Intellectual developmental disorder, autosomal recessive 44, MIM #615942
Prepair 1000+ v1.1989 METTL23 Zornitza Stark Publications for gene: METTL23 were set to
Infertility and Recurrent Pregnancy Loss v0.63 CHEK1 Jasmine Chew edited their review of gene: CHEK1: Changed rating: GREEN
Infertility and Recurrent Pregnancy Loss v0.63 CHEK1 Jasmine Chew gene: CHEK1 was added
gene: CHEK1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: CHEK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHEK1 were set to 33953335; 33948904
Phenotypes for gene: CHEK1 were set to Oocyte/zygote/embryo maturation arrest 21, MIM# 620610
Added comment: Literature in OMIM- PMID: 33953335; 33948904
- >3 unrelated with infertility due to zygote/embryo cleavage arrest with three different missense variants and 1 1bp deletion. Functional studies using transfection studies showed that all mutant increased cytoplasmic localization significantly greater kinase activity. Injection of all mutant cRNA into mouse zygotes with 2 distinct pronuclei also resulted in significantly decreased cleavage rates compared to wildtype.

Note: couldn't find new case reports
Sources: Literature
Prepair 1000+ v1.1988 MEGF10 Zornitza Stark Marked gene: MEGF10 as ready
Prepair 1000+ v1.1988 MEGF10 Zornitza Stark Gene: megf10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1988 MEGF10 Zornitza Stark Phenotypes for gene: MEGF10 were changed from Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, 614399 (3) to Congenital myopathy 10A, severe variant, MIM #614399; Congenital myopathy 10B, mild variant, MIM #620249
Prepair 1000+ v1.1987 MEGF10 Zornitza Stark Publications for gene: MEGF10 were set to
Prepair 1000+ v1.1986 MED12 Zornitza Stark Marked gene: MED12 as ready
Prepair 1000+ v1.1986 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1986 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from Lujan-Fryns syndrome, 309520 (3) to MED12-related intellectual disability syndrome, MONDO:0100000
Prepair 1000+ v1.1985 MED12 Zornitza Stark Publications for gene: MED12 were set to
Prepair 1000+ v1.1984 MBTPS2 Zornitza Stark Marked gene: MBTPS2 as ready
Prepair 1000+ v1.1984 MBTPS2 Zornitza Stark Gene: mbtps2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1984 MBTPS2 Zornitza Stark Phenotypes for gene: MBTPS2 were changed from IFAP syndrome with or without BRESHECK syndrome, 308205 (3) to IFAP syndrome with or without BRESHECK syndrome MIM#308205; Osteogenesis imperfecta, type XIX MIM#301014
Prepair 1000+ v1.1983 MBTPS2 Zornitza Stark Publications for gene: MBTPS2 were set to
Prepair 1000+ v1.1982 MAPKBP1 Zornitza Stark Marked gene: MAPKBP1 as ready
Prepair 1000+ v1.1982 MAPKBP1 Zornitza Stark Gene: mapkbp1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1982 MAPKBP1 Zornitza Stark Phenotypes for gene: MAPKBP1 were changed from Nephronophthisis 20, 617271 (3), Autosomal recessive to Nephronophthisis 20, MIM# 617271; MONDO:0014997
Prepair 1000+ v1.1981 MAPKBP1 Zornitza Stark Publications for gene: MAPKBP1 were set to
Prepair 1000+ v1.1980 LYST Zornitza Stark Marked gene: LYST as ready
Prepair 1000+ v1.1980 LYST Zornitza Stark Gene: lyst has been classified as Green List (High Evidence).
Prepair 1000+ v1.1980 LYST Zornitza Stark Phenotypes for gene: LYST were changed from Chediak-Higashi syndrome, 214500 (3) to Chediak-Higashi syndrome MIM#214500
Prepair 1000+ v1.1979 LYST Zornitza Stark Publications for gene: LYST were set to
Prepair 1000+ v1.1978 LRMDA Zornitza Stark Marked gene: LRMDA as ready
Prepair 1000+ v1.1978 LRMDA Zornitza Stark Gene: lrmda has been classified as Green List (High Evidence).
Prepair 1000+ v1.1978 LRMDA Zornitza Stark Phenotypes for gene: LRMDA were changed from Albinism, oculocutaneous, type VII, 615179 (3) to Albinism, oculocutaneous, type VII MIM#615179; MONDO:0014070
Prepair 1000+ v1.1977 LRMDA Zornitza Stark Publications for gene: LRMDA were set to
Prepair 1000+ v1.1976 LRAT Zornitza Stark Marked gene: LRAT as ready
Prepair 1000+ v1.1976 LRAT Zornitza Stark Gene: lrat has been classified as Green List (High Evidence).
Prepair 1000+ v1.1976 LRAT Zornitza Stark Phenotypes for gene: LRAT were changed from Leber congenital amaurosis 14, 613341 (3) to Retinal dystrophy, early-onset severe; Leber congenital amaurosis 14; Retinitis pigmentosa, juvenile, all under MIM #613341
Prepair 1000+ v1.1975 LRAT Zornitza Stark Publications for gene: LRAT were set to
Prepair 1000+ v1.1974 LONP1 Zornitza Stark Marked gene: LONP1 as ready
Prepair 1000+ v1.1974 LONP1 Zornitza Stark Gene: lonp1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1974 LONP1 Zornitza Stark Phenotypes for gene: LONP1 were changed from CODAS syndrome, 600373 (3) to CODAS syndrome, MIM#600373
Prepair 1000+ v1.1973 LONP1 Zornitza Stark Publications for gene: LONP1 were set to
Prepair 1000+ v1.1972 LMOD3 Zornitza Stark Marked gene: LMOD3 as ready
Prepair 1000+ v1.1972 LMOD3 Zornitza Stark Gene: lmod3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1972 LMOD3 Zornitza Stark Phenotypes for gene: LMOD3 were changed from Nemaline myopathy 10, 616165 (3) to Nemaline myopathy 10, MIM#616165
Prepair 1000+ v1.1971 LMOD3 Zornitza Stark Publications for gene: LMOD3 were set to
Prepair 1000+ v1.1970 LIPC Zornitza Stark Tag for review tag was added to gene: LIPC.
Prepair 1000+ v1.1970 LIPC Zornitza Stark reviewed gene: LIPC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hepatic lipase deficiency, MIM# 614025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1970 LARS2 Zornitza Stark Marked gene: LARS2 as ready
Prepair 1000+ v1.1970 LARS2 Zornitza Stark Gene: lars2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1970 LARS2 Zornitza Stark Phenotypes for gene: LARS2 were changed from Perrault syndrome 4, 615300 (3) to Hydrops, lactic acidosis, and sideroblastic anaemia MIM#617021; Perrault syndrome 4 MIM#615300
Prepair 1000+ v1.1969 LARS2 Zornitza Stark Publications for gene: LARS2 were set to
Prepair 1000+ v1.1968 LAMB2 Zornitza Stark Marked gene: LAMB2 as ready
Prepair 1000+ v1.1968 LAMB2 Zornitza Stark Gene: lamb2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1968 LAMB2 Zornitza Stark Phenotypes for gene: LAMB2 were changed from Pierson syndrome, 609049 (3) to Pierson syndrome, MIM# 609049; Nephrotic syndrome, type 5, with or without ocular abnormalities, MIM# 614199
Prepair 1000+ v1.1967 LAMB2 Zornitza Stark reviewed gene: LAMB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pierson syndrome, MIM# 609049, Nephrotic syndrome, type 5, with or without ocular abnormalities, MIM# 614199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1967 SLC7A7 Lilian Downie Marked gene: SLC7A7 as ready
Prepair 1000+ v1.1967 SLC7A7 Lilian Downie Gene: slc7a7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1967 SLC7A7 Lilian Downie Publications for gene: SLC7A7 were set to
Prepair 1000+ v1.1966 STIM1 Lilian Downie Marked gene: STIM1 as ready
Prepair 1000+ v1.1966 STIM1 Lilian Downie Gene: stim1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1966 STIM1 Lilian Downie Publications for gene: STIM1 were set to
Prepair 1000+ v1.1965 TOE1 Lilian Downie Marked gene: TOE1 as ready
Prepair 1000+ v1.1965 TOE1 Lilian Downie Gene: toe1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1965 TOE1 Lilian Downie Phenotypes for gene: TOE1 were changed from Pontocerebellar hypoplasia, type 7, 614969 (3), Autosomal recessive to Pontocerebellar hypoplasia, type 7 MIM#614969
Prepair 1000+ v1.1964 TOE1 Lilian Downie Publications for gene: TOE1 were set to
Prepair 1000+ v1.1963 TPP1 Lilian Downie Marked gene: TPP1 as ready
Prepair 1000+ v1.1963 TPP1 Lilian Downie Gene: tpp1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1963 TPP1 Lilian Downie Phenotypes for gene: TPP1 were changed from Ceroid lipofuscinosis, neuronal, 2, 204500 (3) to Ceroid lipofuscinosis, neuronal, 2 MIM#204500; Spinocerebellar ataxia, autosomal recessive 7 MIM#609270
Prepair 1000+ v1.1962 TPP1 Lilian Downie Publications for gene: TPP1 were set to
Prepair 1000+ v1.1961 TRAPPC11 Lilian Downie Marked gene: TRAPPC11 as ready
Prepair 1000+ v1.1961 TRAPPC11 Lilian Downie Gene: trappc11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1961 TRAPPC11 Lilian Downie Publications for gene: TRAPPC11 were set to
Prepair 1000+ v1.1960 TRMT10A Lilian Downie Marked gene: TRMT10A as ready
Prepair 1000+ v1.1960 TRMT10A Lilian Downie Gene: trmt10a has been classified as Green List (High Evidence).
Prepair 1000+ v1.1960 TRMT10A Lilian Downie Publications for gene: TRMT10A were set to
Prepair 1000+ v1.1959 UBE3B Lilian Downie Marked gene: UBE3B as ready
Prepair 1000+ v1.1959 UBE3B Lilian Downie Gene: ube3b has been classified as Green List (High Evidence).
Prepair 1000+ v1.1959 UBE3B Lilian Downie Publications for gene: UBE3B were set to
Prepair 1000+ v1.1958 USH1G Lilian Downie Marked gene: USH1G as ready
Prepair 1000+ v1.1958 USH1G Lilian Downie Gene: ush1g has been classified as Green List (High Evidence).
Prepair 1000+ v1.1958 USH1G Lilian Downie Publications for gene: USH1G were set to
Prepair 1000+ v1.1957 VIPAS39 Lilian Downie Marked gene: VIPAS39 as ready
Prepair 1000+ v1.1957 VIPAS39 Lilian Downie Gene: vipas39 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1957 VIPAS39 Lilian Downie Publications for gene: VIPAS39 were set to
Prepair 1000+ v1.1956 VKORC1 Lilian Downie Marked gene: VKORC1 as ready
Prepair 1000+ v1.1956 VKORC1 Lilian Downie Added comment: Comment when marking as ready: Single homozygous missense variant, Arg98Trp reported to cause the AR phenotype (PMID: 12704386). (ClinGen 2023) This phenotype causes intracranial haemmorhage in the first weeks of life and ongoing bleeding predisposition but this is reversed with vit K administration so highly treatable.
Prepair 1000+ v1.1956 VKORC1 Lilian Downie Gene: vkorc1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1956 XRCC4 Lilian Downie Marked gene: XRCC4 as ready
Prepair 1000+ v1.1956 XRCC4 Lilian Downie Gene: xrcc4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1956 XRCC4 Lilian Downie Phenotypes for gene: XRCC4 were changed from Short stature, microcephaly, and endocrine dysfunction, 616541 (3), Autosomal recessive to Short stature, microcephaly, and endocrine dysfunction MIM#616541
Prepair 1000+ v1.1955 XRCC4 Lilian Downie Publications for gene: XRCC4 were set to
Prepair 1000+ v1.1954 XYLT2 Lilian Downie Marked gene: XYLT2 as ready
Prepair 1000+ v1.1954 XYLT2 Lilian Downie Gene: xylt2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1954 XYLT2 Lilian Downie Phenotypes for gene: XYLT2 were changed from Spondyloocular syndrome, 605822 (3), Autosomal recessive to Spondyloocular syndrome MIM#605822
Prepair 1000+ v1.1953 XYLT2 Lilian Downie Publications for gene: XYLT2 were set to
Infertility and Recurrent Pregnancy Loss v0.63 ASTL Jasmine Chew gene: ASTL was added
gene: ASTL was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: ASTL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASTL were set to 34704130; 37640117; 37133443
Phenotypes for gene: ASTL were set to Oocyte/zygote/embryo maturation arrest 11, MIM# 619643
Review for gene: ASTL was set to GREEN
Added comment: Literature in OMIM- PMID: 34704130- One Saudi family with 2 sisters with reduced or absent fertility due to oocyte maturation defect carrying a homozygous splice variant.

New papers (biallelic variants)
i) PMID: 37640117 - Novel compound heterozygous missense variants (p.Arg117Cys and p.Arg274Trp) in a Chinese woman with primary infertility and polyspermy in IVF. Moreover, transfection studies using CHO-K1 cells indicated that mutant cells showed abnormal ovastacin zymogen activation or decreased enzyme stability.

ii) PMID: 37133443- Biallelic variants in four independent affected individuals with primary infertility. The frameshift variants significantly decreased the quantity of ASTL protein in vitro. And all missense variants affected the enzymatic activity that cleaves ZP2 in mouse egg in vitro. Three knock-in female mice (corresponding to three missense variants in patients) all show subfertility due to low embryo developmental potential.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 FOXP3 Jasmine Chew gene: FOXP3 was added
gene: FOXP3 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: FOXP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FOXP3 were set to 28833278; 25546394; 26395338; 26387632; 26009232
Phenotypes for gene: FOXP3 were set to X-linked immunodysregulation, polyendocrinopathy, and enteropathy, MIM# 304790
Review for gene: FOXP3 was set to GREEN
Added comment: Multiple papers reported recurrent male miscarriages in different families:
i) PMID: 28833278- hemizygous truncating variant (p.D303fs*87) in a most recent male IUFD fetus (hydrops fetalis and fetal death around 18 GA weeks) in a family with recurrent IUFD of 19 males in total occurred at ≤20 weeks of gestation, and the same variant was carried by all five healthy obligatory female carriers. Recent studies involving patients with unexplained recurrent spontaneous abortions have demonstrated that downregulation of Treg cells may be due to a significant decrease in the expression of the FOXP3 gene due to epigenetic suppression of FOXP3 through promoter methylation, thus increasing the risk for IUFD (PMID: 27785899)

ii) PMID: 25546394- Two unrelated families with clear evidence of fetal-onset IPEX syndrome (Family 1 had a family history of five miscarriages of males in two generations, positive for hemizygous p.R397W, family 2 with first two males died prematurely after birth and miscarriage of two monochorionic male twins, positive for hemizygous truncating variant (p.S107Nfs*204).

iii) PMID: 26395338- A family with the loss of two male fetuses as a result of fetal hydrops of unknown etiology due to novel nonsense variant (p.R337*).

iv)PMID: 26387632- The same p.R337* in an unrelated family with multiple male miscarriages occurring around 18 to 20 weeks of EGA and associated with hydrops fetalis and fetal akinesia.

v) PMID: 26009232- A family with two miscarriages and three early IUFDs of male fetuses with hemizygous missense variant (p.L345F).
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 STAR Jasmine Chew changed review comment from: Literature on variants associated with ovarian failure presented in unrelated classic lipoid adrenal hyperplasia (LAH) patients:
i) PMID: 38913505- Homozygous p.W147X, p.Arg182Cys, p.W250X, p.Gln258X, p.Leu260Pro, p.Leu275Pro with low/loss of function when tested in vitro.

ii) PMID: 36733346 - Novel compound heterozygous variants (p. Q258*/p. S186R)-p.Q258* generates a truncated protein while S186R disrupts STAR protein function. The residual STAR activities of p.S186R, p.Q258*, and p. S186R/p.Q258* were 13.9%, 7.3%, and 11.2%, respectively, of the wild-type, proving the main negative effects of the mutant proteins.
Sources: Literature; to: Literature on variants associated with ovarian failure presented in unrelated classic lipoid adrenal hyperplasia (LAH) patients:
i) PMID: 38913505- Homozygous p.W147X, p.Arg182Cys, p.W250X, p.Gln258X, p.Leu260Pro, p.Leu275Pro with low/loss of function when tested in vitro.

ii) PMID: 36733346 - Novel compound heterozygous variants (p. Q258*/p. S186R)-p.Q258* generates a truncated protein while S186R disrupts STAR protein function. The residual STAR activities of p.S186R, p.Q258*, and p. S186R/p.Q258* were 13.9%, 7.3%, and 11.2%, of the wild-type protein activity, respectively.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 STAR Jasmine Chew gene: STAR was added
gene: STAR was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: STAR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAR were set to 38913505; 36733346
Phenotypes for gene: STAR were set to Lipoid adrenal hyperplasia, MIM# 201710
Review for gene: STAR was set to GREEN
Added comment: Literature on variants associated with ovarian failure presented in unrelated classic lipoid adrenal hyperplasia (LAH) patients:
i) PMID: 38913505- Homozygous p.W147X, p.Arg182Cys, p.W250X, p.Gln258X, p.Leu260Pro, p.Leu275Pro with low/loss of function when tested in vitro.

ii) PMID: 36733346 - Novel compound heterozygous variants (p. Q258*/p. S186R)-p.Q258* generates a truncated protein while S186R disrupts STAR protein function. The residual STAR activities of p.S186R, p.Q258*, and p. S186R/p.Q258* were 13.9%, 7.3%, and 11.2%, respectively, of the wild-type, proving the main negative effects of the mutant proteins.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 SYCE1 Jasmine Chew changed review comment from: Literature in OMIM: PMIM: 25062452; 25899990; 26203179- biallelic variants reported for affected individuals with POI/spermatogenic failure (NOA)

New papers (biallelic variants for POI/NOA):
i) PMID: 36373164- Two POI/DOR patients with biallelic LOF variants (Patient II-1 in Family 3 with compound heterozygous variants c.154C > T (p.Arg52*) and c.675del (p.Asp226Metfs*29); Patient II-1 in Family 6 with a homozygous donor splicing variant c.271 + 1G > A which led to exon 4 skipping and indel mutant p.Ala66_Leu91delinsVal).

ii) PMID: 35718780- Two NOA-affected patients with different biallelic CNVs (patient 1- novel heterozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135111754_135427143del) and heterozygous LOF (p.F230fs), patient 2- homozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135340247_135379115del).

iii) PMID: 34718620- Compound heterozygous variants (p.Glu159Lys and p.Phe230Serfs*21) in a POI patient and a homozygous variant (NM_001143764.3: c.271 + 2T > C) in a NOA patient.
Sources: Literature; to: Literature in OMIM: PMIM: 25062452; 25899990; 26203179- biallelic variants reported for affected individuals with POI/spermatogenic failure (NOA)

New papers (biallelic variants for POI/NOA):
i) PMID: 36373164- Two POI/DOR patients with biallelic LOF variants (Patient II-1 in Family 3 with compound heterozygous variants c.154C > T (p.Arg52*) and c.675del (p.Asp226Metfs*29); Patient II-1 in Family 6 with a homozygous donor splicing variant c.271 + 1G > A which led to exon 4 skipping and indel mutant p.Ala66_Leu91delinsVal).

ii) PMID: 35718780- Two NOA-affected patients with different biallelic CNVs (patient 1- novel heterozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135111754_135427143del) and heterozygous LOF (p.F230fs), patient 2- homozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135340247_135379115del).

iii) PMID: 34718620- Compound heterozygous variants (p.Glu159Lys and p.Phe230Serfs*21) in a POI patient and a homozygous variant (NM_001143764.3: c.271 + 2T > C) in a NOA patient.
Sources: Literature
Mode of pathogenicity: Provide exceptions to loss-of-function
Infertility and Recurrent Pregnancy Loss v0.63 SYCE1 Jasmine Chew edited their review of gene: SYCE1: Changed mode of pathogenicity: Other; Changed phenotypes: Premature ovarian failure 12, MIM# 616947, Spermatogenic failure 15 ,MIM# 616950
Infertility and Recurrent Pregnancy Loss v0.63 SYCE1 Jasmine Chew edited their review of gene: SYCE1: Changed phenotypes: Premature ovarian failure 12, MIM# 616947, Spermatogenic failure 15 ,MIM#616950
Infertility and Recurrent Pregnancy Loss v0.63 SYCE1 Jasmine Chew changed review comment from: Literature in OMIM: PMIM: 25062452; 25899990; 26203179- biallelic variants reported for affected individuals with POI/spermatogenic failure (NOA)

New papers (biallelic variants for POI/NOA):
i) PMID: 36373164- Two POI/DOR patients with biallelic LOF variants (Patient II-1 in Family 3 with compound heterozygous variants c.154C > T (p.Arg52*) and c.675del (p.Asp226Metfs*29); Patient II-1 in Family 6 with a homozygous donor splicing variant c.271 + 1G > A which led to exon 4 skipping and indel mutant p.Ala66_Leu91delinsVal).

ii) PMID: 35718780- Two NOA-affected patients with different biallelic CNVs (patient 1- novel heterozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135111754_135427143del) and heterozygous LOF (p.F230fs), patient 2- homozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135340247_135379115del).

iii) PMID: 34718620- Compound heterozygous variants (p.Glu159Lys and p.Phe230Serfs*21) in a POI patient and a homozygous variant (NM_001143764.3: c.271 + 2T > C) in a NOA patient.
Sources: Literature; to: Literature in OMIM: PMIM: 25062452; 25899990; 26203179- biallelic variants reported for affected individuals with POI/spermatogenic failure (NOA)

New papers (biallelic variants for POI/NOA):
i) PMID: 36373164- Two POI/DOR patients with biallelic LOF variants (Patient II-1 in Family 3 with compound heterozygous variants c.154C > T (p.Arg52*) and c.675del (p.Asp226Metfs*29); Patient II-1 in Family 6 with a homozygous donor splicing variant c.271 + 1G > A which led to exon 4 skipping and indel mutant p.Ala66_Leu91delinsVal).

ii) PMID: 35718780- Two NOA-affected patients with different biallelic CNVs (patient 1- novel heterozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135111754_135427143del) and heterozygous LOF (p.F230fs), patient 2- homozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135340247_135379115del).

iii) PMID: 34718620- Compound heterozygous variants (p.Glu159Lys and p.Phe230Serfs*21) in a POI patient and a homozygous variant (NM_001143764.3: c.271 + 2T > C) in a NOA patient.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 SYCE1 Jasmine Chew gene: SYCE1 was added
gene: SYCE1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: SYCE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SYCE1 were set to 25062452; 25899990; 26203179; 36373164; 35718780; 34718620
Phenotypes for gene: SYCE1 were set to Premature ovarian failure 12, MIM# 616947, Spermatogenic failure 15 ,MIM# 616950
Mode of pathogenicity for gene: SYCE1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: SYCE1 was set to GREEN
Added comment: Literature in OMIM: PMIM: 25062452; 25899990; 26203179- biallelic variants reported for affected individuals with POI/spermatogenic failure (NOA)

New papers (biallelic variants for POI/NOA):
i) PMID: 36373164- Two POI/DOR patients with biallelic LOF variants (Patient II-1 in Family 3 with compound heterozygous variants c.154C > T (p.Arg52*) and c.675del (p.Asp226Metfs*29); Patient II-1 in Family 6 with a homozygous donor splicing variant c.271 + 1G > A which led to exon 4 skipping and indel mutant p.Ala66_Leu91delinsVal).

ii) PMID: 35718780- Two NOA-affected patients with different biallelic CNVs (patient 1- novel heterozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135111754_135427143del) and heterozygous LOF (p.F230fs), patient 2- homozygous intragenic deletion (seq[GRCh37] del(10)(10q26.3)chr10:g.135340247_135379115del).

iii) PMID: 34718620- Compound heterozygous variants (p.Glu159Lys and p.Phe230Serfs*21) in a POI patient and a homozygous variant (NM_001143764.3: c.271 + 2T > C) in a NOA patient.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 WT1 Jasmine Chew gene: WT1 was added
gene: WT1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: WT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WT1 were set to 26358501; 34845858
Phenotypes for gene: WT1 were set to Primary ovarian failure, MONDO:0005387
Review for gene: WT1 was set to GREEN
Added comment: New papers reported variants associated with POI:
i) PMID: 26358501- Two novel heterozygous missense variants (p. Pro126Ser in exon1 and p. Arg370His in exon7) in two unrelated POI patients, and functional study on these two missense variants showed in impaired transcription of downstream genes, including AMH, FSHR, CYP19 and CDH.

ii) PMID: 34845858- A de novo heterozygous nonsense variant p.R463* in a non-syndromic POI woman. Western blot analysis further demonstrated that the WT1 variant could produce a truncated WT1 isoform in vitro.
Sources: Literature
Prepair 1000+ v1.1952 KIF7 Zornitza Stark Marked gene: KIF7 as ready
Prepair 1000+ v1.1952 KIF7 Zornitza Stark Gene: kif7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1952 KIF7 Zornitza Stark Phenotypes for gene: KIF7 were changed from Hydrolethalus syndrome 2, 614120 (3) to Al-Gazali-Bakalinova syndrome MIM#607131; Hydrolethalus syndrome 2 MIM#614120; Acrocallosal syndrome MIM#200990; Joubert syndrome 12 MIM#200990
Prepair 1000+ v1.1951 KIF7 Zornitza Stark Publications for gene: KIF7 were set to
Prepair 1000+ v1.1950 KIAA1109 Zornitza Stark Marked gene: KIAA1109 as ready
Prepair 1000+ v1.1950 KIAA1109 Zornitza Stark Gene: kiaa1109 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1950 KIAA1109 Zornitza Stark Phenotypes for gene: KIAA1109 were changed from Alkuraya-Kucinskas syndrome, 617822 (3), Autosomal recessive to Alkuraya-Kucinskas syndrome MIM#617822
Prepair 1000+ v1.1949 KIAA1109 Zornitza Stark Publications for gene: KIAA1109 were set to
Prepair 1000+ v1.1948 KIAA1109 Zornitza Stark Tag new gene name tag was added to gene: KIAA1109.
Prepair 1000+ v1.1948 KCNV2 Zornitza Stark Marked gene: KCNV2 as ready
Prepair 1000+ v1.1948 KCNV2 Zornitza Stark Gene: kcnv2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1948 KCNV2 Zornitza Stark Phenotypes for gene: KCNV2 were changed from Retinal cone dystrophy 3B, 610356 (3) to Retinal cone dystrophy 3B MIM#610356
Prepair 1000+ v1.1947 KCNV2 Zornitza Stark Publications for gene: KCNV2 were set to
Prepair 1000+ v1.1946 ITK Zornitza Stark Marked gene: ITK as ready
Prepair 1000+ v1.1946 ITK Zornitza Stark Gene: itk has been classified as Green List (High Evidence).
Prepair 1000+ v1.1946 ITK Zornitza Stark Phenotypes for gene: ITK were changed from Lymphoproliferative syndrome 1, 613011 (3) to Lymphoproliferative syndrome 1 MIM# 613011
Prepair 1000+ v1.1945 ITK Zornitza Stark Publications for gene: ITK were set to
Prepair 1000+ v1.1944 ITK Zornitza Stark changed review comment from: Established gene-disease association characterized by onset in early childhood of Epstein-Barr virus (EBV)-associated immune dysregulation, manifest as lymphoma, lymphomatoid granulomatosis, haemophagocytic lymphohistiocytosis, Hodgkin disease, and/or hypogammaglobulinaemia. Autoimmune disorders, such as autoimmune haemolytic anemia or renal disease, may also occur.; to: Established gene-disease association characterized by onset in early childhood of Epstein-Barr virus (EBV)-associated immune dysregulation, manifest as lymphoma, lymphomatoid granulomatosis, haemophagocytic lymphohistiocytosis, Hodgkin disease, and/or hypogammaglobulinaemia. Autoimmune disorders, such as autoimmune haemolytic anaemia or renal disease, may also occur.
Prepair 1000+ v1.1944 ITK Zornitza Stark reviewed gene: ITK: Rating: GREEN; Mode of pathogenicity: None; Publications: 19425169, 22289921, 25061172, 26056787, 9311799, 10213685; Phenotypes: Lymphoproliferative syndrome 1 MIM# 613011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1944 INVS Zornitza Stark Marked gene: INVS as ready
Prepair 1000+ v1.1944 INVS Zornitza Stark Gene: invs has been classified as Green List (High Evidence).
Prepair 1000+ v1.1944 INVS Zornitza Stark Phenotypes for gene: INVS were changed from Nephronophthisis 2, infantile, 602088 (3) to Nephronophthisis 2, infantile, (MIM#602088)
Prepair 1000+ v1.1943 INVS Zornitza Stark reviewed gene: INVS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephronophthisis 2, infantile, (MIM#602088); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1943 INPP5K Zornitza Stark Marked gene: INPP5K as ready
Prepair 1000+ v1.1943 INPP5K Zornitza Stark Gene: inpp5k has been classified as Green List (High Evidence).
Prepair 1000+ v1.1943 INPP5K Zornitza Stark Phenotypes for gene: INPP5K were changed from Muscular dystrophy, congenital, with cataracts and intellectual disability, 617404 (3), Autosomal recessive to Muscular dystrophy, congenital, with cataracts and intellectual disability MIM#617404
Prepair 1000+ v1.1942 INPP5K Zornitza Stark Publications for gene: INPP5K were set to
Prepair 1000+ v1.1941 INPP5K Zornitza Stark Tag founder tag was added to gene: INPP5K.
Prepair 1000+ v1.1941 IFT172 Zornitza Stark Marked gene: IFT172 as ready
Prepair 1000+ v1.1941 IFT172 Zornitza Stark Gene: ift172 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1941 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from Short-rib thoracic dysplasia 10 with or without polydactyly, 615630 (3) to Bardet-Biedl syndrome 20 MIM#619471; Retinitis pigmentosa 71 MIM#616394; Short-rib thoracic dysplasia 10 with or without polydactyly MIM#615630
Prepair 1000+ v1.1940 IFT172 Zornitza Stark Publications for gene: IFT172 were set to
Prepair 1000+ v1.1939 IDUA Zornitza Stark Marked gene: IDUA as ready
Prepair 1000+ v1.1939 IDUA Zornitza Stark Gene: idua has been classified as Green List (High Evidence).
Prepair 1000+ v1.1939 IDUA Zornitza Stark Phenotypes for gene: IDUA were changed from Mucopolysaccharidosis Ih, 607014 (3) to Mucopolysaccharidosis Ih/s (Hurler syndrome) 607014
Prepair 1000+ v1.1938 IDUA Zornitza Stark reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis Ih/s (Hurler syndrome) 607014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1938 IBA57 Zornitza Stark Marked gene: IBA57 as ready
Prepair 1000+ v1.1938 IBA57 Zornitza Stark Gene: iba57 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1938 IBA57 Zornitza Stark Phenotypes for gene: IBA57 were changed from Multiple mitochondrial dysfunctions syndrome 3, 615330 (3), Autosomal recessive to Multiple mitochondrial dysfunctions syndrome 3 MIM#615330
Prepair 1000+ v1.1937 IBA57 Zornitza Stark Publications for gene: IBA57 were set to
Prepair 1000+ v1.1936 HYLS1 Zornitza Stark Marked gene: HYLS1 as ready
Prepair 1000+ v1.1936 HYLS1 Zornitza Stark Gene: hyls1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1936 HYLS1 Zornitza Stark Phenotypes for gene: HYLS1 were changed from Hydrolethalus syndrome, 236680 (3) to Hydrolethalus syndrome (MIM#236680)
Prepair 1000+ v1.1935 HYLS1 Zornitza Stark Publications for gene: HYLS1 were set to
Prepair 1000+ v1.1934 HSPD1 Zornitza Stark Marked gene: HSPD1 as ready
Prepair 1000+ v1.1934 HSPD1 Zornitza Stark Gene: hspd1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1934 HSPD1 Zornitza Stark Phenotypes for gene: HSPD1 were changed from Leukodystrophy, hypomyelinating, 4, 612233 (3) to Leukodystrophy, hypomyelinating, 4 MIM#612233
Prepair 1000+ v1.1933 HSPD1 Zornitza Stark Publications for gene: HSPD1 were set to
Prepair 1000+ v1.1932 HSD3B7 Zornitza Stark edited their review of gene: HSD3B7: Changed publications: 27604308
Prepair 1000+ v1.1932 HSD3B7 Zornitza Stark Marked gene: HSD3B7 as ready
Prepair 1000+ v1.1932 HSD3B7 Zornitza Stark Gene: hsd3b7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1932 HSD3B7 Zornitza Stark Publications for gene: HSD3B7 were set to
Prepair 1000+ v1.1931 HSD3B7 Zornitza Stark Phenotypes for gene: HSD3B7 were changed from Bile acid synthesis defect, congenital, 1, 607765 (3) to Bile acid synthesis defect, congenital, 1 MIM#607765
Prepair 1000+ v1.1930 HSD3B7 Zornitza Stark reviewed gene: HSD3B7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bile acid synthesis defect, congenital, 1 MIM#607765; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1930 HPS3 Zornitza Stark Marked gene: HPS3 as ready
Prepair 1000+ v1.1930 HPS3 Zornitza Stark Gene: hps3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1930 HPS3 Zornitza Stark Phenotypes for gene: HPS3 were changed from Hermansky-Pudlak syndrome 3, 614072 (3) to Hermansky-Pudlak syndrome 3 MIM#614072
Prepair 1000+ v1.1929 HPS3 Zornitza Stark Publications for gene: HPS3 were set to
Prepair 1000+ v1.1928 HAMP Zornitza Stark Marked gene: HAMP as ready
Prepair 1000+ v1.1928 HAMP Zornitza Stark Gene: hamp has been classified as Green List (High Evidence).
Prepair 1000+ v1.1928 HAMP Zornitza Stark Phenotypes for gene: HAMP were changed from Hemochromatosis, type 2B, 613313 (3) to Haemochromatosis, type 2B MIM#613313
Prepair 1000+ v1.1927 HAMP Zornitza Stark Publications for gene: HAMP were set to
Prepair 1000+ v1.1926 HADH Zornitza Stark Marked gene: HADH as ready
Prepair 1000+ v1.1926 HADH Zornitza Stark Gene: hadh has been classified as Green List (High Evidence).
Prepair 1000+ v1.1926 HADH Zornitza Stark Phenotypes for gene: HADH were changed from 3-hydroxyacyl-CoA dehydrogenase deficiency, 231530 (3) to 3-hydroxyacyl-CoA dehydrogenase deficiency MIM#231530
Prepair 1000+ v1.1925 HADH Zornitza Stark Publications for gene: HADH were set to
Prepair 1000+ v1.1924 GM2A Zornitza Stark Marked gene: GM2A as ready
Prepair 1000+ v1.1924 GM2A Zornitza Stark Gene: gm2a has been classified as Green List (High Evidence).
Prepair 1000+ v1.1924 GM2A Zornitza Stark Phenotypes for gene: GM2A were changed from GM2-gangliosidosis, AB variant, 272750 (3) to GM2-gangliosidosis, AB variant MIM #272750
Prepair 1000+ v1.1923 GM2A Zornitza Stark Publications for gene: GM2A were set to
Prepair 1000+ v1.1922 GLDN Zornitza Stark Marked gene: GLDN as ready
Prepair 1000+ v1.1922 GLDN Zornitza Stark Gene: gldn has been classified as Green List (High Evidence).
Prepair 1000+ v1.1922 GLDN Zornitza Stark Phenotypes for gene: GLDN were changed from Lethal congenital contracture syndrome 11, 617194 (3), Autosomal recessive to Lethal congenital contracture syndrome 11 MIM#617194
Prepair 1000+ v1.1921 GLDN Zornitza Stark Publications for gene: GLDN were set to
Prepair 1000+ v1.1920 FYCO1 Zornitza Stark Marked gene: FYCO1 as ready
Prepair 1000+ v1.1920 FYCO1 Zornitza Stark Gene: fyco1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1920 FYCO1 Zornitza Stark Phenotypes for gene: FYCO1 were changed from Cataract 18, autosomal recessive, 610019 (3) to Cataract 18, MIM#610019
Prepair 1000+ v1.1919 FYCO1 Zornitza Stark reviewed gene: FYCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cataract 18, MIM#610019; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1919 FTSJ1 Zornitza Stark Marked gene: FTSJ1 as ready
Prepair 1000+ v1.1919 FTSJ1 Zornitza Stark Gene: ftsj1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1919 FTSJ1 Zornitza Stark Phenotypes for gene: FTSJ1 were changed from Mental retardation, X-linked 9, 309549 (3) to Intellectual developmental disorder, X-linked 9 MIM#309549
Prepair 1000+ v1.1918 FTSJ1 Zornitza Stark Publications for gene: FTSJ1 were set to
Prepair 1000+ v1.1917 FRAS1 Zornitza Stark Marked gene: FRAS1 as ready
Prepair 1000+ v1.1917 FRAS1 Zornitza Stark Gene: fras1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1917 FRAS1 Zornitza Stark Phenotypes for gene: FRAS1 were changed from Fraser syndrome, 219000 (3) to Fraser syndrome 1 MIM#219000
Prepair 1000+ v1.1916 FRAS1 Zornitza Stark Publications for gene: FRAS1 were set to
Prepair 1000+ v1.1915 FLAD1 Zornitza Stark Marked gene: FLAD1 as ready
Prepair 1000+ v1.1915 FLAD1 Zornitza Stark Gene: flad1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1915 FLAD1 Zornitza Stark Phenotypes for gene: FLAD1 were changed from Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency, 255100 (3), Autosomal recessive to Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency MIM#255100
Prepair 1000+ v1.1914 FLAD1 Zornitza Stark Publications for gene: FLAD1 were set to
Prepair 1000+ v1.1913 FLAD1 Zornitza Stark reviewed gene: FLAD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34454814, 34718578, 31392824, 30982706, 30311138, 30427553, 28433476, 27259049, 25058219; Phenotypes: Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency MIM#255100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1913 FKBP14 Zornitza Stark Marked gene: FKBP14 as ready
Prepair 1000+ v1.1913 FKBP14 Zornitza Stark Gene: fkbp14 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1913 FKBP14 Zornitza Stark Phenotypes for gene: FKBP14 were changed from Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss, 614557 (3) to Ehlers-Danlos syndrome, kyphoscoliotic type, 2 MIM#614557
Prepair 1000+ v1.1912 FKBP14 Zornitza Stark Publications for gene: FKBP14 were set to
Prepair 1000+ v1.1911 FHL1 Zornitza Stark Marked gene: FHL1 as ready
Prepair 1000+ v1.1911 FHL1 Zornitza Stark Gene: fhl1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1911 FHL1 Zornitza Stark Phenotypes for gene: FHL1 were changed from Emery-Dreifuss muscular dystrophy 6, X-linked, 300696 (3) to Reducing body myopathy MONDO:0019948; X-linked Emery-Dreifuss muscular dystrophy MONDO:0010680
Prepair 1000+ v1.1910 FHL1 Zornitza Stark Publications for gene: FHL1 were set to
Prepair 1000+ v1.1909 FHL1 Zornitza Stark Mode of inheritance for gene: FHL1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.1908 FGD4 Zornitza Stark Marked gene: FGD4 as ready
Prepair 1000+ v1.1908 FGD4 Zornitza Stark Gene: fgd4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1908 FGD4 Zornitza Stark Phenotypes for gene: FGD4 were changed from Charcot-Marie-Tooth disease, type 4H, 609311 (3) to Charcot-Marie-Tooth disease, type 4H MIM#609311; Charcot-Marie-Tooth disease MONDO:0015626
Prepair 1000+ v1.1907 FGD4 Zornitza Stark Publications for gene: FGD4 were set to
Prepair 1000+ v1.1906 FANCL Zornitza Stark Marked gene: FANCL as ready
Prepair 1000+ v1.1906 FANCL Zornitza Stark Gene: fancl has been classified as Green List (High Evidence).
Prepair 1000+ v1.1906 FANCL Zornitza Stark Phenotypes for gene: FANCL were changed from Fanconi anemia, complementation group L, 614083 (3) to Fanconi anaemia, complementation group L MIM#614083
Prepair 1000+ v1.1905 FANCL Zornitza Stark Publications for gene: FANCL were set to
Prepair 1000+ v1.1904 FANCD2 Zornitza Stark Marked gene: FANCD2 as ready
Prepair 1000+ v1.1904 FANCD2 Zornitza Stark Gene: fancd2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1904 FANCD2 Zornitza Stark Phenotypes for gene: FANCD2 were changed from Fanconi anemia, complementation group D2, 227646 (3) to Fanconi anaemia, complementation group D2 MIM#227646
Prepair 1000+ v1.1903 FANCD2 Zornitza Stark Publications for gene: FANCD2 were set to
Prepair 1000+ v1.1902 ERCC4 Zornitza Stark Marked gene: ERCC4 as ready
Prepair 1000+ v1.1902 ERCC4 Zornitza Stark Gene: ercc4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1902 ERCC4 Zornitza Stark Phenotypes for gene: ERCC4 were changed from Fanconi anemia, complementation group Q, 615272 (3) to Fanconi anemia, complementation group Q, MIM# 615272 MONDO:0014108; Xeroderma pigmentosum, group F, MIM# 278760 MONDO:0010215; XFE progeroid syndrome, MIM# 610965 MONDO:0012590
Prepair 1000+ v1.1901 ERCC4 Zornitza Stark reviewed gene: ERCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group Q, MIM# 615272 MONDO:0014108, Xeroderma pigmentosum, group F, MIM# 278760 MONDO:0010215, XFE progeroid syndrome, MIM# 610965 MONDO:0012590; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1901 DOLK Zornitza Stark Marked gene: DOLK as ready
Prepair 1000+ v1.1901 DOLK Zornitza Stark Gene: dolk has been classified as Green List (High Evidence).
Prepair 1000+ v1.1901 DOLK Zornitza Stark Phenotypes for gene: DOLK were changed from Congenital disorder of glycosylation, type Im, 610768 (3) to Congenital disorder of glycosylation, type Im, MIM# 610768
Prepair 1000+ v1.1900 DOLK Zornitza Stark Publications for gene: DOLK were set to
Prepair 1000+ v1.1899 DOLK Zornitza Stark reviewed gene: DOLK: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273964, 22242004, 23890587, 30653653, 28816422, 24144945; Phenotypes: Congenital disorder of glycosylation, type Im, MIM# 610768; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1899 COL11A2 Zornitza Stark Marked gene: COL11A2 as ready
Prepair 1000+ v1.1899 COL11A2 Zornitza Stark Added comment: Comment when marking as ready: Deafness currently out of scope for this panel.
Prepair 1000+ v1.1899 COL11A2 Zornitza Stark Gene: col11a2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1899 COL11A2 Zornitza Stark Phenotypes for gene: COL11A2 were changed from Fibrochondrogenesis 2, 614524 (3) to Fibrochondrogenesis 2 MIM#614524
Prepair 1000+ v1.1898 COL11A2 Zornitza Stark Publications for gene: COL11A2 were set to
Prepair 1000+ v1.1897 AGK Zornitza Stark Marked gene: AGK as ready
Prepair 1000+ v1.1897 AGK Zornitza Stark Gene: agk has been classified as Green List (High Evidence).
Prepair 1000+ v1.1897 AGK Zornitza Stark Phenotypes for gene: AGK were changed from Sengers syndrome, 212350 (3) to Sengers syndrome, MIM#212350
Prepair 1000+ v1.1896 AGK Zornitza Stark reviewed gene: AGK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sengers syndrome, MIM#212350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2481 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781; {Polycystic kidney disease 9, susceptibility to} MIM#621164 to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781; {Polycystic kidney disease 9, susceptibility to} MIM#621164; Cranioectodermal dysplasia 5, MIM# 621180
Mendeliome v1.2480 IFT140 Zornitza Stark Publications for gene: IFT140 were set to 34890546; 22503633; 23418020; 28288023; 28724397; 26216056; 26968735
Mendeliome v1.2479 IFT140 Zornitza Stark edited their review of gene: IFT140: Added comment: Four unrelated families reported with biallelic variants and a cranioectrodermal dysplasia phenotype, part of the ciliopathy spectrum.; Changed publications: 22503633, 23418020, 28288023, 28724397, 26216056, 26968735, 32007091, 35873489, 37628605; Changed phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, Retinitis pigmentosa 80, MIM# 617781, {Polycystic kidney disease 9, susceptibility to} MIM#621164, Cranioectodermal dysplasia 5, MIM# 621180
Ciliopathies v1.66 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781; Cystic Kidney Disease, MONDO: 0002473, IFT140-associated, dominant; Cranioectodermal dysplasia 5, MIM# 621180 to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781; Cystic Kidney Disease, MONDO: 0002473, IFT140-associated, dominant; Cranioectodermal dysplasia 5, MIM# 621180
Ciliopathies v1.65 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781; Cystic Kidney Disease, MONDO: 0002473, IFT140-associated, dominant to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781; Cystic Kidney Disease, MONDO: 0002473, IFT140-associated, dominant; Cranioectodermal dysplasia 5, MIM# 621180
Ciliopathies v1.64 IFT140 Zornitza Stark Publications for gene: IFT140 were set to 22503633; 23418020; 28288023; 28724397; 26216056; 26968735; 34890546
Ciliopathies v1.63 IFT140 Zornitza Stark edited their review of gene: IFT140: Added comment: Four unrelated families reported with biallelic variants and a cranioectrodermal dysplasia phenotype, part of the ciliopathy spectrum.; Changed publications: 22503633, 23418020, 28288023, 28724397, 26216056, 26968735, 34890546, 32007091, 35873489, 37628605; Changed phenotypes: Cystic Kidney Disease, MONDO: 0002473, IFT140-associated, dominant, Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, Retinitis pigmentosa 80, MIM# 617781, Cranioectodermal dysplasia 5, MIM# 621180
Genetic Epilepsy v1.126 USP25 Sangavi Sivagnanasundram reviewed gene: USP25: Rating: AMBER; Mode of pathogenicity: Other; Publications: 38875478; Phenotypes: USP25-related epilepsy (epilepsy MONDO:0005027); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2479 USP25 Sangavi Sivagnanasundram edited their review of gene: USP25: Added comment: This gene-disease association has been DISPUTED by ClinGen Epilepsy GCEP on 01/04/2025 - https://search.clinicalgenome.org/CCID:008786

ClinGen's reason for disuputed classification - "Case-level data was not considered strong enough to score. Functional data was not consistent among the variants and was difficult to interpret in relationship to a seizure phenotype. The knock-out mouse model did not exhibit spontaneous seizures so was not scored."

Downgrade to Amber due to the uncertainty was agreed within the user group.; Changed rating: AMBER; Changed phenotypes: USP25-related epilepsy (epilepsy MONDO:0005027)
Mendeliome v1.2479 FOXM1 Achchuthan Shanmugasundram gene: FOXM1 was added
gene: FOXM1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXM1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXM1 were set to 38969938
Phenotypes for gene: FOXM1 were set to Moyamoya disease, MONDO:0016820
Review for gene: FOXM1 was set to AMBER
Added comment: PMID:38969938 reported a 60-year-old father and 31-year-old daughter with unilateral Moyamoya Disease and with c.1205 C > A variant in FOXM1 gene (p.(Ala402Glu). There is also functional evidence available for the identified variant from the publication. This gene should be rated amber with current evidence.
Sources: Literature
Hereditary Neuropathy_CMT - isolated v1.52 NARS Chris Ciotta changed review comment from: Three families reported in the literature with heterozygous NARS1 variants and an isolated peripheral neuropathy phenotype, lacking the global developmental delay, seizures and intellectual disability and more seen in the dominant and recessive neurodevelopmental disorder phenotypes listed in OMIM (MIM#619091 and MIM#619092).

Beijer (2024) (PMID: 38495304): Two families with previously unreported missense variants and an isolated neuropathy phenotype. Segregation of this variant with disease also shown. Both missense variants severely reduced yeast growth compared to wildtype in a yeast rescue complementation assay. A mouse model expressing the p.Ser461Phe variant did not show any signs of peripheral neuropathy in mice heterozygous for this variant at multiple time points to 18 months of age.

Theuriet (2024) (PMID: 38769024): A novel missense reported in a French family with distal hereditary motor neuropathy. A mother and two sons all with an isolated phenotype with no seizures or ID. Mother presented in 30s and two sons presented 5 and 3 with toe walking. A yeast model was also done here with this variant allowing for no growth compared to wildtype.
Sources: Literature; to: Three families reported in the literature with heterozygous NARS1 variants and an isolated peripheral neuropathy phenotype, lacking the global developmental delay, seizures and intellectual disability and more seen in the dominant and recessive neurodevelopmental disorder phenotypes listed in OMIM (MIM#619091 and MIM#619092).

Beijer (2024) (PMID: 38495304): Two families with previously unreported missense variants and an isolated neuropathy phenotype. Segregation of these variants with disease also shown. Both missense variants severely reduced yeast growth compared to wildtype in a yeast rescue complementation assay. A mouse model expressing the p.Ser461Phe variant did not show any signs of peripheral neuropathy in mice heterozygous for this variant at multiple time points to 18 months of age.

Theuriet (2024) (PMID: 38769024): A novel missense reported in a French family with distal hereditary motor neuropathy. A mother and two sons all with an isolated phenotype with no seizures or ID. Mother presented in 30s and two sons presented 5 and 3 with toe walking. A yeast model was also done here with this variant allowing for no growth compared to wildtype.
Sources: Literature
Hereditary Neuropathy_CMT - isolated v1.52 NARS Chris Ciotta gene: NARS was added
gene: NARS was added to Hereditary Neuropathy_CMT - isolated. Sources: Literature
Mode of inheritance for gene: NARS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NARS were set to PMID: 38495304; 38769024
Phenotypes for gene: NARS were set to Axonal neuropathy; Charcot-Marie-Tooth disease; distal hereditary motor neuropathy
Review for gene: NARS was set to AMBER
Added comment: Three families reported in the literature with heterozygous NARS1 variants and an isolated peripheral neuropathy phenotype, lacking the global developmental delay, seizures and intellectual disability and more seen in the dominant and recessive neurodevelopmental disorder phenotypes listed in OMIM (MIM#619091 and MIM#619092).

Beijer (2024) (PMID: 38495304): Two families with previously unreported missense variants and an isolated neuropathy phenotype. Segregation of this variant with disease also shown. Both missense variants severely reduced yeast growth compared to wildtype in a yeast rescue complementation assay. A mouse model expressing the p.Ser461Phe variant did not show any signs of peripheral neuropathy in mice heterozygous for this variant at multiple time points to 18 months of age.

Theuriet (2024) (PMID: 38769024): A novel missense reported in a French family with distal hereditary motor neuropathy. A mother and two sons all with an isolated phenotype with no seizures or ID. Mother presented in 30s and two sons presented 5 and 3 with toe walking. A yeast model was also done here with this variant allowing for no growth compared to wildtype.
Sources: Literature
Prepair 1000+ v1.1896 SLC37A4 Lilian Downie Marked gene: SLC37A4 as ready
Prepair 1000+ v1.1896 SLC37A4 Lilian Downie Gene: slc37a4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1896 SLC37A4 Lilian Downie Phenotypes for gene: SLC37A4 were changed from Glycogen storage disease Ib, 232220 (3) to Glycogen storage disease Ib MIM#232220; Glycogen storage disease Ic MIM#232240; Glycogen Storage Disease I MONDO:0002413
Prepair 1000+ v1.1895 SP110 Lilian Downie Marked gene: SP110 as ready
Prepair 1000+ v1.1895 SP110 Lilian Downie Gene: sp110 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1895 SP110 Lilian Downie Publications for gene: SP110 were set to
Prepair 1000+ v1.1894 SPR Lilian Downie Marked gene: SPR as ready
Prepair 1000+ v1.1894 SPR Lilian Downie Gene: spr has been classified as Green List (High Evidence).
Prepair 1000+ v1.1894 SPR Lilian Downie Phenotypes for gene: SPR were changed from Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716 (3) to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency MIM#612716
Prepair 1000+ v1.1893 SPR Lilian Downie Publications for gene: SPR were set to
Prepair 1000+ v1.1892 STRA6 Lilian Downie Marked gene: STRA6 as ready
Prepair 1000+ v1.1892 STRA6 Lilian Downie Gene: stra6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1892 STRA6 Lilian Downie Phenotypes for gene: STRA6 were changed from Microphthalmia MIM#601186 to Microphthalmia, isolated, with coloboma 8 MIM#601186; Microphthalmia, syndromic 9 MIM#601186
Prepair 1000+ v1.1891 STRA6 Lilian Downie Phenotypes for gene: STRA6 were changed from Microphthalmia, isolated, with coloboma 8, 601186 (3) to Microphthalmia MIM#601186
Mendeliome v1.2479 B3GALT6 Sangavi Sivagnanasundram reviewed gene: B3GALT6: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008674; Phenotypes: B3GALT6-congenital disorder of glycosylation MONDO:0100586; Mode of inheritance: None
Prepair 1000+ v1.1890 STRA6 Lilian Downie Publications for gene: STRA6 were set to
Prepair 1000+ v1.1889 TRIM32 Lilian Downie Marked gene: TRIM32 as ready
Prepair 1000+ v1.1889 TRIM32 Lilian Downie Gene: trim32 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1889 TRIM32 Lilian Downie Phenotypes for gene: TRIM32 were changed from Muscular dystrophy, limb-girdle, type 2H, 254110 (3) to Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110
Prepair 1000+ v1.1888 TRIM32 Lilian Downie Publications for gene: TRIM32 were set to
Prepair 1000+ v1.1887 TRPM6 Lilian Downie Marked gene: TRPM6 as ready
Prepair 1000+ v1.1887 TRPM6 Lilian Downie Gene: trpm6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1887 TRPM6 Lilian Downie Publications for gene: TRPM6 were set to
Prepair 1000+ v1.1886 TTI2 Lilian Downie Marked gene: TTI2 as ready
Prepair 1000+ v1.1886 TTI2 Lilian Downie Gene: tti2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1886 TTI2 Lilian Downie Phenotypes for gene: TTI2 were changed from Mental retardation, autosomal recessive 39, 615541 (3) to Intellectual developmental disorder, autosomal recessive 39 MIM#615541
Mendeliome v1.2479 PIK3R5 Sangavi Sivagnanasundram reviewed gene: PIK3R5: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008779; Phenotypes: ataxia with oculomotor apraxia type 3 MONDO:0014084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1885 TTI2 Lilian Downie Publications for gene: TTI2 were set to
Prepair 1000+ v1.1884 TTPA Lilian Downie Marked gene: TTPA as ready
Prepair 1000+ v1.1884 TTPA Lilian Downie Gene: ttpa has been classified as Green List (High Evidence).
Prepair 1000+ v1.1884 TTPA Lilian Downie Publications for gene: TTPA were set to
Prepair 1000+ v1.1883 VARS Lilian Downie Marked gene: VARS as ready
Prepair 1000+ v1.1883 VARS Lilian Downie Gene: vars has been classified as Green List (High Evidence).
Prepair 1000+ v1.1883 VARS Lilian Downie Phenotypes for gene: VARS were changed from Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy, 617802 (3), Autosomal recessive to Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy MIM#617802
Prepair 1000+ v1.1882 VARS Lilian Downie Publications for gene: VARS were set to
Mendeliome v1.2479 PCNA Sangavi Sivagnanasundram gene: PCNA was added
gene: PCNA was added to Mendeliome. Sources: ClinGen
Mode of inheritance for gene: PCNA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCNA were set to 24911150, 33426167, 36990216
Phenotypes for gene: PCNA were set to hereditary ataxia MONDO:0100309
Review for gene: PCNA was set to AMBER
Added comment: Classified as Limited by Cerebellar Ataxia GCEP on 09/04/2025 - https://search.clinicalgenome.org/CCID:008778

Two missense variants have been reported across 5 families. Both the missense variants are present in gnomAD (rare enough for AR gene). Method of pathogenicity is still unknown.
Affected individuals reported with ataxia, photosensitivity, telangiectasias, and some degree of intellectual disability.
Sources: ClinGen
Prepair 1000+ v1.1881 WNT10B Lilian Downie Marked gene: WNT10B as ready
Prepair 1000+ v1.1881 WNT10B Lilian Downie Gene: wnt10b has been classified as Green List (High Evidence).
Prepair 1000+ v1.1881 WNT10B Lilian Downie Publications for gene: WNT10B were set to
Prepair 1000+ v1.1880 CSPP1 Lilian Downie Marked gene: CSPP1 as ready
Prepair 1000+ v1.1880 CSPP1 Lilian Downie Gene: cspp1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1880 CSPP1 Lilian Downie Phenotypes for gene: CSPP1 were changed from Joubert syndrome 21, 615636 (3) to Joubert syndrome 21 MIM#615636; MONDO:0014288
Prepair 1000+ v1.1879 CSPP1 Lilian Downie Publications for gene: CSPP1 were set to
Prepair 1000+ v1.1878 DNAH5 Lilian Downie Marked gene: DNAH5 as ready
Prepair 1000+ v1.1878 DNAH5 Lilian Downie Gene: dnah5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1878 DNAH5 Lilian Downie Publications for gene: DNAH5 were set to
Prepair 1000+ v1.1877 PEX5 Lilian Downie Marked gene: PEX5 as ready
Prepair 1000+ v1.1877 PEX5 Lilian Downie Gene: pex5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1877 PEX5 Lilian Downie Phenotypes for gene: PEX5 were changed from Peroxisome biogenesis disorder 2A (Zellweger), 214110 to Peroxisome Biogenesis Disorder, MONDO:0019234
Prepair 1000+ v1.1876 PEX5 Lilian Downie Publications for gene: PEX5 were set to 21031596; 7719337; 26220973; 20301621
Prepair 1000+ v1.1875 PEX5 Lilian Downie Publications for gene: PEX5 were set to
Prepair 1000+ v1.1874 PIGN Lilian Downie Marked gene: PIGN as ready
Prepair 1000+ v1.1874 PIGN Lilian Downie Gene: pign has been classified as Green List (High Evidence).
Prepair 1000+ v1.1874 PIGN Lilian Downie Publications for gene: PIGN were set to
Prepair 1000+ v1.1873 PLAA Lilian Downie Marked gene: PLAA as ready
Prepair 1000+ v1.1873 PLAA Lilian Downie Gene: plaa has been classified as Green List (High Evidence).
Prepair 1000+ v1.1873 PLAA Lilian Downie Phenotypes for gene: PLAA were changed from Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, 617527 (3), Autosomal recessive to Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies,MIM#617527
Prepair 1000+ v1.1872 PLAA Lilian Downie Publications for gene: PLAA were set to
Prepair 1000+ v1.1871 PLCE1 Lilian Downie Marked gene: PLCE1 as ready
Prepair 1000+ v1.1871 PLCE1 Lilian Downie Gene: plce1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1871 PLCE1 Lilian Downie Publications for gene: PLCE1 were set to
Prepair 1000+ v1.1870 POLR3B Lilian Downie Marked gene: POLR3B as ready
Prepair 1000+ v1.1870 POLR3B Lilian Downie Gene: polr3b has been classified as Green List (High Evidence).
Prepair 1000+ v1.1870 POLR3B Lilian Downie Mode of pathogenicity for gene: POLR3B was changed from to None
Prepair 1000+ v1.1869 POLR3B Lilian Downie Publications for gene: POLR3B were set to
Mendeliome v1.2479 ANKZF1 Sangavi Sivagnanasundram reviewed gene: ANKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008790; Phenotypes: inflammatory bowel disease MONDO:0005265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.124 ANKZF1 Sangavi Sivagnanasundram reviewed gene: ANKZF1: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008790; Phenotypes: inflammatory bowel disease MONDO:0005265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic Diabetes v0.137 SIRT1 Sangavi Sivagnanasundram gene: SIRT1 was added
gene: SIRT1 was added to Monogenic Diabetes. Sources: ClinGen
Mode of inheritance for gene: SIRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIRT1 were set to https://search.clinicalgenome.org/CCID:008794
Phenotypes for gene: SIRT1 were set to monogenic diabetes MONDO:0015967
Review for gene: SIRT1 was set to RED
Added comment: Classified as LIMITED by Monogenic Diabetes GCEP on 18/04/2025 - https://search.clinicalgenome.org/CCID:008794
Sources: ClinGen
Mendeliome v1.2479 SIRT1 Sangavi Sivagnanasundram reviewed gene: SIRT1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008794; Phenotypes: monogenic diabetes MONDO:0015967; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: ICoNS v0.0 Zornitza Stark Added Panel Genomic newborn screening: ICoNS
Genomic newborn screening: BabyScreen+ v1.117 Zornitza Stark Panel name changed from BabyScreen+ newborn screening to Genomic newborn screening: BabyScreen+
Mendeliome v1.2479 FGFR3 Bryony Thompson Mode of inheritance for gene: FGFR3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.2478 FGFR1 Bryony Thompson Publications for gene: FGFR1 were set to 18034870; 23812909; 26942290; 16470795; 15625620; 29147600; 20339250
Mendeliome v1.2477 FGFR1 Bryony Thompson Publications for gene: FGFR1 were set to 18034870; 23812909; 26942290
Infertility and Recurrent Pregnancy Loss v0.63 PANX1 Jasmine Chew gene: PANX1 was added
gene: PANX1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: PANX1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: PANX1 were set to 30918116; 39232764; 35834089; 36469255; 33495594
Phenotypes for gene: PANX1 were set to Oocyte/zygote/embryo maturation arrest 7, MIM# 618550
Review for gene: PANX1 was set to GREEN
Added comment: Literature in OMIM- PMID: 30918116: 4 different monoallelic variants in 4 unrelated Chinese families with 8 women who were infertile due to oocyte death. Functional analysis demonstrated that the mutations alter the PANX1 glycosylation pattern, influence subcellular localization, and increase channel activity and ATP release.

New papers-
i) PMID: 39232764;35834089;36469255- 3 novel monoallelic variants (p.Ser137Leu,p. Arg29Gln, p.Asn326del) causing human oocyte death and female infertility. Western blot analysis confirmed that Arg29Gln and p.Asn326del changed the glycosylation pattern in HeLa cells.

ii) PMID: 33495594- two novel homozygous missense variants associated with the oocyte death phenotype in two families. Both of the homozygous variants altered the PANX1 glycosylation pattern in cultured cells, led to aberrant PANX1 channel activation, and resulted in mouse oocyte death after fertilization in vitro. It is worth noting that the destructive effect of the two homozygous variants on PANX1 function was weaker than that caused by the recently reported heterozygous variants.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 TRIP13 Jasmine Chew gene: TRIP13 was added
gene: TRIP13 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: TRIP13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIP13 were set to 32473092; 28553959; 35812326
Phenotypes for gene: TRIP13 were set to Oocyte/zygote/embryo maturation arrest 9, #MIM 619011; Mosaic variegated aneuploidy syndrome 3, #MIM 617598
Review for gene: TRIP13 was set to GREEN
Added comment: Literature in OMIM- PMID: 32473092;28553959- different biallelic variants in >3 unrelated affected individuals

New papers:
i) PMID: 35812326- Two women with zygotic cleavage failure (ZCF) carrying homozygous p. Glu381Lys and compound heterozygous p. Lys420Glu and p. His26Arg. All three variants resulted in obvious changes in hydrogen bonding and consistent increase in DNA damage. Additionally, transcriptomic sequencing of oocytes and arrested embryos containing these variants suggested a greater number of differentially expressed transcripts in germinal vesicle (GV) oocytes than in 1-cell embryos.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 FBXO43 Jasmine Chew gene: FBXO43 was added
gene: FBXO43 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: FBXO43 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBXO43 were set to 34052850; 30878252; 34595750
Phenotypes for gene: FBXO43 were set to Oocyte/zygote/embryo maturation arrest 12, MIM# 619697; Spermatogenic failure 64, MIM# 619696
Review for gene: FBXO43 was set to GREEN
Added comment: Literature in OMIM: PMID: 34052850 (three different homozygous variants in 3 unrelated women; 30878252, 34595750 (two different families with different homozygous variants)
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 FGA Jasmine Chew gene: FGA was added
gene: FGA was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: FGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGA were set to 29016666; 34925444
Phenotypes for gene: FGA were set to Recurrent pregnancy loss
Review for gene: FGA was set to GREEN
Added comment: i) PMID: 29016666- A heterozygous missense p.Phe685Cys called pathogenic in a female with RPL (3 miscarriages, all embryonic loss) and fragment molecular orbital analysis showed that the p.F685C variant led to changes in total interaction energy, thus leading to protein instability

ii) PMID: 34925444: Two heterozygous FGA variants were identified in two women, each with three consecutive miscarriages- one variant (NM_000508.5: c.1906_1908del; p.636del) leading to the deletion of an amino acid was not found in public databases. The other variant in FGA (p.A762V) causing an amino acid substitution was extremely rare in East Asian populations in the gnomAD database and was predicted to be deleterious by in silico prediction tools.
- " Mutations of FGA have been linked to coagulation pathologies including afibrinogenemia (OMIM:202400) and dysfibrinogenemia/hypodysfibrinogenemia (OMIM:616004), which can result in miscarriage (PMID: 31368232).
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 KHDC3L Jasmine Chew changed review comment from: Biallelic variants have been reported for several unrelated families with recurrent complete hydatidiform mole (CHM) pregnancy- predominantly biparental and RPL- PMID: 21885028, 19246479, 23232697.

New evidence-
i) PMID 31847873: homozygous LOF variant in a woman with multiple consanguineous marriages in her extended family and history of 2 biparental complete hydatidiform mole (BiCHM) and methylation study on her oocytes revealed a genome-wide deficit of DNA methylation compared with normal human oocytes.

ii) PMID: 31609975- two deletions of KHDC3L (p.E150_V160del and p.E150_V172del) in female RPL patients, both of which harbor a common loss of Thr156 and are impaired in PARP1 activation and homologous recombination (HR) repair. Also provided functional evidence that KHDC3L dysfunction causes PARP1 inhibition and HR-mediated DNA repair deficiency, which is synthetically lethal.

iii) PMID: 29606347- a novel homozygous frameshift p.Q15Rfs*25 variant in a female patient (II-1) from family 4 with a history of 2 spontaneous abortions and x2 partial hydatidiform moles, and her embryos formed after ICSI are fertilized normally but arrest at the morula stage.
Sources: Literature; to: Biallelic variants have been reported for several unrelated families with recurrent complete hydatidiform mole (CHM) pregnancy- predominantly biparental and RPL- PMID: 21885028, 19246479, 23232697.

New evidence (biallelic variants and CHM pregnancy)-
i) PMID 31847873: homozygous LOF variant in a woman with multiple consanguineous marriages in her extended family and history of 2 biparental complete hydatidiform mole (BiCHM) and methylation study on her oocytes revealed a genome-wide deficit of DNA methylation compared with normal human oocytes.

ii) PMID: 31609975- two deletions of KHDC3L (p.E150_V160del and p.E150_V172del) in female RPL patients, both of which harbor a common loss of Thr156 and are impaired in PARP1 activation and homologous recombination (HR) repair. Also provided functional evidence that KHDC3L dysfunction causes PARP1 inhibition and HR-mediated DNA repair deficiency, which is synthetically lethal.

iii) PMID: 29606347- a novel homozygous frameshift p.Q15Rfs*25 variant in a female patient (II-1) from family 4 with a history of 2 spontaneous abortions and x2 partial hydatidiform moles, and her embryos formed after ICSI are fertilized normally but arrest at the morula stage.

New evidence (monoallelic variants and RPL)-
i) PMID: 34925444- a heterozygous in frame deletion in KHDC3L (p.146_156del) in a 31-year-old woman with a history of two miscarriages.
ii) PMID: 31609975- heterozygous deletions (p.150_160del and p.150_172del) were found in patients experiencing RPL without forming an hydatidiform mole.
Note: All of the deletions in patients with RPL affected the Thr156 residue, a critical phosphorylation site for normal KHDC3L protein function. Loss of Thr156 results in impaired PARP1 activation and HR repair.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 KHDC3L Jasmine Chew edited their review of gene: KHDC3L: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2476 FGF8 Bryony Thompson Publications for gene: FGF8 were set to 34433009; 32664970; 7768185; 32664970; 10603341; 19509466; 9462741; 10603341; 12223415
Mendeliome v1.2475 FGF8 Bryony Thompson Publications for gene: FGF8 were set to 34433009
Mendeliome v1.2474 FGA Bryony Thompson Publications for gene: FGA were set to 31064749; 17295221; 19073821; 11739173
Mendeliome v1.2473 FGA Bryony Thompson Mode of inheritance for gene: FGA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.55 FGA Bryony Thompson Mode of inheritance for gene: FGA was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.54 FGB Bryony Thompson Publications for gene: FGB were set to 12393540; 16195396; 24560896
Bleeding and Platelet Disorders v1.54 FGB Bryony Thompson Publications for gene: FGB were set to 12393540; 16195396
Bleeding and Platelet Disorders v1.53 FGB Bryony Thompson Mode of inheritance for gene: FGB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Bleeding and Platelet Disorders v1.52 FGB Bryony Thompson reviewed gene: FGB: Rating: GREEN; Mode of pathogenicity: None; Publications: 24560896; Phenotypes: Congenital fibrinogen deficiency MONDO:0018060; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.2472 FGB Bryony Thompson Publications for gene: FGB were set to 12393540; 16195396
Mendeliome v1.2471 FGB Bryony Thompson Mode of inheritance for gene: FGB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.2470 FGB Bryony Thompson reviewed gene: FGB: Rating: GREEN; Mode of pathogenicity: None; Publications: 24560896; Phenotypes: Congenital fibrinogen deficiency MONDO:0018060; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.2470 FGA Bryony Thompson reviewed gene: FGA: Rating: GREEN; Mode of pathogenicity: None; Publications: 10602365, 11460510; Phenotypes: Congenital fibrinogen deficiency MONDO:0018060; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Bleeding and Platelet Disorders v1.52 FGA Bryony Thompson edited their review of gene: FGA: Changed rating: GREEN
Bleeding and Platelet Disorders v1.52 FGA Bryony Thompson reviewed gene: FGA: Rating: ; Mode of pathogenicity: None; Publications: 10602365, 11460510; Phenotypes: Congenital fibrinogen deficiency MONDO:0018060; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.2470 FAR1 Bryony Thompson reviewed gene: FAR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33586168, 25439727; Phenotypes: Fatty acyl-CoA reductase 1 deficiency MONDO:0014510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.2470 FANCM Bryony Thompson edited their review of gene: FANCM: Added comment: Now 4 families with biallelic variants reported with spermatogenic failure; Changed publications: 29231814, 28837162, 33036707, 25010009, 38927643, 35413094, 30075111, 29895858; Changed phenotypes: Premature ovarian failure 15 MIM#618096, spermatogenic failure 28 MONDO:0054732; Set current diagnostic: yes
Mendeliome v1.2470 FANCI Bryony Thompson Publications for gene: FANCI were set to 17452773
Bleeding and Platelet Disorders v1.52 F9 Bryony Thompson changed review comment from: Classified as LIMITED by the Hemostasis Thrombosis GCEP in 2023 with 2 families reported with missense variants, however 3 additional families/cases have been reported with increased factor 9 activity and large duplications involving F9. Gain of function is the mechanism of disease for the thrombophilia.; to: Classified as LIMITED by the Hemostasis Thrombosis GCEP in 2023 with 2 families reported with missense variants; however, 3 additional families/cases have been reported with increased factor 9 activity and large duplications involving F9. Gain of function is the mechanism of disease for thrombophilia.
Mendeliome v1.2469 F9 Bryony Thompson reviewed gene: F9: Rating: GREEN; Mode of pathogenicity: Other; Publications: 19846852, 32079698, 38886735, 38358900, 37414287, 33656538; Phenotypes: thrombophilia, X-linked, due to factor 9 defect MONDO:0010432; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.2469 F9 Bryony Thompson Publications for gene: F9 were set to 19846852; 34015304; 33656538; 3001143; 9016521; 19815722
Bleeding and Platelet Disorders v1.52 F9 Bryony Thompson edited their review of gene: F9: Changed mode of pathogenicity: Other
Bleeding and Platelet Disorders v1.52 F9 Bryony Thompson reviewed gene: F9: Rating: GREEN; Mode of pathogenicity: None; Publications: 19846852, 32079698, 38886735, 38358900, 37414287, 33656538; Phenotypes: thrombophilia, X-linked, due to factor 9 defect MONDO:0010432; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.2468 F9 Bryony Thompson Publications for gene: F9 were set to 19846852; 34015304; 33656538
Mendeliome v1.2467 F5 Bryony Thompson Publications for gene: F5 were set to
Mendeliome v1.2466 F2 Bryony Thompson Classified gene: F2 as Green List (high evidence)
Mendeliome v1.2466 F2 Bryony Thompson Added comment: Comment on list classification: Gain of function is the mechanism of disease for dominant thrombophilia, and biallelic loss of function is the mechanism for congenital prothrombin deficiency.
Mendeliome v1.2466 F2 Bryony Thompson Gene: f2 has been classified as Green List (High Evidence).
Mendeliome v1.2465 F2 Bryony Thompson Tag 5'UTR was removed from gene: F2.
Tag UTR tag was added to gene: F2.
Mendeliome v1.2465 F2 Bryony Thompson Publications for gene: F2 were set to 30297698
Infertility and Recurrent Pregnancy Loss v0.63 ZFP36L2 Jasmine Chew gene: ZFP36L2 was added
gene: ZFP36L2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: ZFP36L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFP36L2 were set to 34611029; 38829516; 37211617
Phenotypes for gene: ZFP36L2 were set to Oocyte/zygote/embryo maturation arrest 13, MIM# 620154
Review for gene: ZFP36L2 was set to GREEN
Added comment: i) Literature in OMIM- PMID:34611029- x2 unrelated infertile Chinese women with defective oocyte maturation carrying different biallelic variants and functional analysis suggested that the variants cause maternal mRNA decay defects that result in female infertility.

ii) New papers reporting biallelic variants in conjunction with female infertility due to oocyte maturation defect+/- embryonic development arrest
- PMID: 38829516: Novel compound heterozygous variant (p.His62Gln and p.Pro290Leu) in a patient with oocyte maturation defect. These variants lead to compromised binding capacity of the ZFP36L2-CONT6L complex and impaired mRNA degradation in HeLa cells and mouse oocytes.
- PMID: 37211617: Novel homozygous variant c.853_861del (p.285_287del) in the affected individual with oocyte maturation defect from a consanguineous family. In vitro studies showed that the variant caused decreased protein levels of ZFP36L2 in oocytes due to mRNA instability and might lead to the loss of its function to degrade maternal mRNAs
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 REC114 Jasmine Chew gene: REC114 was added
gene: REC114 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: REC114 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: REC114 were set to 31704776; 30388401; 38148155
Phenotypes for gene: REC114 were set to Oocyte/zygote/embryo maturation arrest 10, #MIM 619176
Review for gene: REC114 was set to GREEN
Added comment: i) Literature in OMIM (PMID: 31704776;30388401)- x3 unrelated females with different biallelic variants presented with infertility due to oocyte maturation defects/multiple pronuclei zygotes, early embryonic arrest, and failed implantation of surviving embryos/miscarriages/recurrent hydatidiform moles.

ii) New paper on male infertility:
- PMID: 38148155- First report that identifies REC114 as the causative gene for male infertility- homozygous p.Gln190* variant in a Chinese NOA patient. Co-immunoprecipitation (Co-IP) and Western blot (WB) revealed that the variant resulted in truncated REC114 protein and impaired interaction with MEI4, which was essential for meiotic DNA double-strand break (DSB) formation.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 WEE2 Jasmine Chew gene: WEE2 was added
gene: WEE2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: WEE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WEE2 were set to 29606300; 30628060; 39476306; 37772619; 36568932; 34476630
Phenotypes for gene: WEE2 were set to Oocyte/zygote/embryo maturation arrest 5, MIM# 617996
Review for gene: WEE2 was set to GREEN
Added comment: i) Literature in OMIM- PMID: 29606300;30628060- >3 unrelated infertile women (e.g., oocyte maturation defect, recurrent fertilization failure) with different biallelic variants

ii) Many other new papers reporting biallelic variants in conjunction with oocyte degradation +/- unexplained fertilization failure - PMID: 39476306;37772619;36568932;34476630

iii) definitive evidence for OZEMA in FeRGI database
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 TLE6 Jasmine Chew changed review comment from: i) Literature in OMIM (PMID:26537248)- 3 women from 2 consanguineous Saudi families with primary infertility due to preimplantation embryonic lethality carrying homozygous missense variant, S510Y. ). Functional analysis demonstrated that the variant abrogates TLE6 phosphorylation by PKA and also impairs TLE6 binding to components of the SCMC.

ii) New papers:
- PMID: 31897846- novel biallelic variants (2 homozygous, 1 compound heterozygous) in 3 patients with recurrent IVF/ICSI failure.
- PMID: 40225929- novel compound heterozygous (c.541+2dupT in intron 7 and c.1075G>A) in a female with embryonic developmental arrest (EDA). The splice variant resulted in aberrant RNA splicing, leading to abnormal truncations of the corresponding proteins. In vitro experiments further validated that the missense variant in NLRP5 led to increased mRNA and protein expression levels compared to wild type, when transfected into HEK293T cells.
- PMID: 32172300- A homozygous truncating variant p.(Lys146Glufs*51) in a patient with recurrent pregnancy loss, and demonstrates that oocytes depleted for TLE6 have the capacity to undergo several postfertilization divisions prior to arrest, consistent with what was observed in Tle6-/- mice (Yu et al. 2014)

iii) Classified as definitive for OZEMA in FeRGI database
Sources: Literature; to: i) Literature in OMIM (PMID:26537248)- 3 women from 2 consanguineous Saudi families with primary infertility due to preimplantation embryonic lethality carrying homozygous missense variant, S510Y). Functional analysis demonstrated that the variant abrogates TLE6 phosphorylation by PKA and also impairs TLE6 binding to components of the SCMC.

ii) New papers:
- PMID: 31897846- novel biallelic variants (2 homozygous, 1 compound heterozygous) in 3 patients with recurrent IVF/ICSI failure.
- PMID: 40225929- novel compound heterozygous (c.541+2dupT in intron 7 and c.1075G>A) in a female with embryonic developmental arrest (EDA). The splice variant resulted in aberrant RNA splicing, leading to abnormal truncations of the corresponding proteins. In vitro experiments further validated that the missense variant in NLRP5 led to increased mRNA and protein expression levels compared to wild type, when transfected into HEK293T cells.
- PMID: 32172300- A homozygous truncating variant p.(Lys146Glufs*51) in a patient with recurrent pregnancy loss, and demonstrates that oocytes depleted for TLE6 have the capacity to undergo several postfertilization divisions prior to arrest, consistent with what was observed in Tle6-/- mice (Yu et al. 2014).

iii) Classified as definitive for OZEMA in FeRGI database
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 TLE6 Jasmine Chew gene: TLE6 was added
gene: TLE6 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: TLE6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TLE6 were set to 26537248; 31897846; 40225929; 32172300
Phenotypes for gene: TLE6 were set to Oocyte/zygote/embryo maturation arrest 15, #MIM 616814
Review for gene: TLE6 was set to GREEN
Added comment: i) Literature in OMIM (PMID:26537248)- 3 women from 2 consanguineous Saudi families with primary infertility due to preimplantation embryonic lethality carrying homozygous missense variant, S510Y. ). Functional analysis demonstrated that the variant abrogates TLE6 phosphorylation by PKA and also impairs TLE6 binding to components of the SCMC.

ii) New papers:
- PMID: 31897846- novel biallelic variants (2 homozygous, 1 compound heterozygous) in 3 patients with recurrent IVF/ICSI failure.
- PMID: 40225929- novel compound heterozygous (c.541+2dupT in intron 7 and c.1075G>A) in a female with embryonic developmental arrest (EDA). The splice variant resulted in aberrant RNA splicing, leading to abnormal truncations of the corresponding proteins. In vitro experiments further validated that the missense variant in NLRP5 led to increased mRNA and protein expression levels compared to wild type, when transfected into HEK293T cells.
- PMID: 32172300- A homozygous truncating variant p.(Lys146Glufs*51) in a patient with recurrent pregnancy loss, and demonstrates that oocytes depleted for TLE6 have the capacity to undergo several postfertilization divisions prior to arrest, consistent with what was observed in Tle6-/- mice (Yu et al. 2014)

iii) Classified as definitive for OZEMA in FeRGI database
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 PABPC1L Jasmine Chew gene: PABPC1L was added
gene: PABPC1L was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: PABPC1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PABPC1L were set to 37052235; 37723834; 38177974; 32172300
Phenotypes for gene: PABPC1L were set to Oocyte/zygote/embryo maturation arrest 22, #MIM 621093
Review for gene: PABPC1L was set to GREEN
Added comment: i) Literature in OMIM (PMID: 37052235;37723834;38177974)- >3 unrelated infertile women (due to a mixed phenotype including oocyte maturation abnormalities, fertilization failure, and embryonic development arrest) with different biallelic variants

ii) Additional paper (PMID: 32172300)- Homozygous likely deleterious variant in PABPC1L p.(Met26Lys) in a woman whose infertility phenotype resembles that of Pabpc1l−/− mouse. During her IVF cycles, 18 oocytes were retrieved and subjected to IVF and ICSI. Nine oocytes were assigned to ICSI, but eight were at germinal vesicle stage and only one showed polar body and failed to fertilize following ICSI. Similarly, nine oocytes were assigned to IVF, and only two showed polar body on the next day without any sign of fertilization. The remaining oocytes were at germinal vesicle stage.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 NLRP7 Jasmine Chew gene: NLRP7 was added
gene: NLRP7 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: NLRP7 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NLRP7 were set to 17579354; 19650864; 25097207; 23201303; 23722513; 32172300; 37148315
Phenotypes for gene: NLRP7 were set to Recurrent hydatidiform mole 1, # MIM 231090
Review for gene: NLRP7 was set to GREEN
Added comment: i) The association between diploid biparental hydatidiform mole (HM), miscarriages, and infertility has been observed in many patients with biallelic functional variants in NLRP7 and some of their HM were diagnosed by morphology as non-molar miscarriages, partial HM (because of their mild trophoblastic proliferation), non-classical HM [PMID: 23201303], or not easy to classify HM [PMID: 23722513].
ii) classified as strong evidence for HM on the FeRGI database
iii) New paper- PMID: 32172300- homozygous truncating variant p.(Lys619Asnfs*18) in an individual with recurrent molar pregnancy and no pregnancy observed following three intra-uterine insemination attempts.
iv) New phenotype (AD):
- PMID: 37148315- five heterozygous variants (c.251G > A, c.1258G > A, c.1441G > A, c. 2227G > A, c.2323C > T) of NLRP7 were identified in five infertile patients who experienced early embryo arrest. Injecting complementary RNAs in mouse oocytes and early embryos showed that NLRP7 variants influenced the oocyte quality and some of the variants significantly affected early embryo development.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.63 DNAH11 Jasmine Chew gene: DNAH11 was added
gene: DNAH11 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: DNAH11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH11 were set to 39256880; 32172300
Phenotypes for gene: DNAH11 were set to Ciliary dyskinesia, primary, 7, with or without situs inversus, # MIM 611884
Added comment: i) PMID: 39256880- Four unrelated asthenoteratozoospermia Chinese males with biallelic deleterious variants in the DNAH11 gene, and 7 of those variants are novel. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated.

ii) PMID: 32172300- One infertile woman with a homozygous truncating variant, p.(Arg3229Trp), presented with primary infertility only. She had three cycles of IVF and had one clinical pregnancy that, unfortunately, ended in a spontaneous loss during first trimester.
Sources: Literature
Renal Macrocystic Disease v0.83 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Cystic Kidney Disease, MONDO# 0002473 to {Polycystic kidney disease 9, susceptibility to} MIM#621164
Renal Macrocystic Disease v0.82 IFT140 Zornitza Stark reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: {Polycystic kidney disease 9, susceptibility to} MIM#621164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Ciliopathies and Nephronophthisis v1.27 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Cystic Kidney Disease, MONDO# 0002473, IFT140-related, dominant to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; {Polycystic kidney disease 9, susceptibility to} MIM#621164
Renal Ciliopathies and Nephronophthisis v1.26 IFT140 Zornitza Stark edited their review of gene: IFT140: Changed phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, MONDO:0009964, {Polycystic kidney disease 9, susceptibility to} MIM#621164
Mendeliome v1.2464 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781; Cystic Kidney Disease, MONDO: 0002473 to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781; {Polycystic kidney disease 9, susceptibility to} MIM#621164
Mendeliome v1.2463 IFT140 Zornitza Stark edited their review of gene: IFT140: Changed phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, Retinitis pigmentosa 80, MIM# 617781, {Polycystic kidney disease 9, susceptibility to} MIM#621164
Prepair 1000+ v1.1868 POLR3B Karina Sandoval reviewed gene: POLR3B: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 27512013, 23355746, 22036171, 22036172, 25339210, 33005949, 22855961, 33417887; Phenotypes: Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism,MIM#614381; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PLCE1 Karina Sandoval reviewed gene: PLCE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17086182, 18065803, 20591883; Phenotypes: Nephrotic syndrome, type 3,MIM#610725; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PLAA Karina Sandoval reviewed gene: PLAA: Rating: GREEN; Mode of pathogenicity: None; Publications: 28007986, 28413018, 31322726; Phenotypes: Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies,MIM#617527; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PIGN Karina Sandoval reviewed gene: PIGN: Rating: GREEN; Mode of pathogenicity: None; Publications: 21493957, 24253414, 26364997, 26394714, 33193741, 32585529, 33528536, 38693247, 36322149; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 1,MIM#614080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PEX5 Karina Sandoval reviewed gene: PEX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 21031596, 7719337, 26220973, 20301621; Phenotypes: Peroxisome Biogenesis Disorder, MONDO:0019234; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2463 EYA4 Bryony Thompson reviewed gene: EYA4: Rating: AMBER; Mode of pathogenicity: None; Publications: 10769282, 30155266, 33745059; Phenotypes: dilated cardiomyopathy 1J MONDO:0011541; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.1868 DNAH5 Andrew Coventry reviewed gene: DNAH5: Rating: GREEN; Mode of pathogenicity: None; Publications: 16627867, 11788826, 40033371; Phenotypes: Ciliary dyskinesia, primary, 3, with or without situs inversus MIM#608644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 CSPP1 Andrew Coventry reviewed gene: CSPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24360808, 24360803, 24360807, 25997910; Phenotypes: Joubert syndrome 21 MIM#615636, MONDO:0014288; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 WNT10B Andrew Coventry reviewed gene: WNT10B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20635353, 16688749, 29427788, 24211389, 38058757, 39310870; Phenotypes: Split-hand/foot malformation 6 MIM#225300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 VARS Andrew Coventry reviewed gene: VARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 30755616, 30755602, 26539891, 29691655, 30275004, 30755616; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy MIM#617802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 TTPA Andrew Coventry reviewed gene: TTPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 27604308, 7719340; Phenotypes: Ataxia with isolated vitamin E deficiency MIM#277460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 TTI2 Andrew Coventry reviewed gene: TTI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32061250, 23956177, 31737043; Phenotypes: Intellectual developmental disorder, autosomal recessive 39 MIM#615541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 TRPM6 Andrew Coventry reviewed gene: TRPM6: Rating: GREEN; Mode of pathogenicity: None; Publications: 35903165, 18818955; Phenotypes: Hypomagnesemia 1, intestinal MIM#602014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 TRIM32 Andrew Coventry reviewed gene: TRIM32: Rating: GREEN; Mode of pathogenicity: None; Publications: 9634523, 10399877, 17994549, 25351777, 19492423, 19303295, 31309175; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2463 ERLIN2 Bryony Thompson Mode of inheritance for gene: ERLIN2 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 STRA6 Andrew Coventry reviewed gene: STRA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273977, 17503335, 19213032, 26373900, 30880327, 26373900, 25457163; Phenotypes: Microphthalmia, isolated, with coloboma 8 MIM#601186, Microphthalmia, syndromic 9 MIM#601186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v1.29 ERLIN2 Bryony Thompson Marked gene: ERLIN2 as ready
Motor Neurone Disease v1.29 ERLIN2 Bryony Thompson Gene: erlin2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1868 SPR Andrew Coventry reviewed gene: SPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 22522443, 26131547, 33903016, 31777525, 16650784, 21431957, 28189489; Phenotypes: Dystonia, dopa-responsive, due to sepiapterin reductase deficiency MIM#612716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v1.29 ERLIN2 Bryony Thompson Classified gene: ERLIN2 as Green List (high evidence)
Motor Neurone Disease v1.29 ERLIN2 Bryony Thompson Gene: erlin2 has been classified as Green List (High Evidence).
Motor Neurone Disease v1.28 ERLIN2 Bryony Thompson gene: ERLIN2 was added
gene: ERLIN2 was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for gene: ERLIN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ERLIN2 were set to 38607533; 38427163; 34734492; 32042907
Phenotypes for gene: ERLIN2 were set to hereditary spastic paraplegia 18 MONDO:0012639
Review for gene: ERLIN2 was set to GREEN
gene: ERLIN2 was marked as current diagnostic
Added comment: HSP phenoconversion to ALS has been reported in AD and AR families.
Sources: Literature
Prepair 1000+ v1.1868 SP110 Andrew Coventry reviewed gene: SP110: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301448, 16648851, 23448538, 22621957, 32395362; Phenotypes: Hepatic venoocclusive disease with immunodeficiency MIM#235550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 SLC37A4 Andrew Coventry reviewed gene: SLC37A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33964207, 9675154, 9758626; Phenotypes: Glycogen storage disease Ib MIM#232220, Glycogen storage disease Ic MIM#232240, Glycogen Storage Disease I MONDO:0002413; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2462 ERLIN2 Bryony Thompson edited their review of gene: ERLIN2: Added comment: AR and AD variants appear to have a different mechanism of disease. AR is presumably loss of function. The mechanism of disease for AD HSP is expected to be dominant negative but has not been confirmed; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 SLC12A5 Andrew Coventry reviewed gene: SLC12A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 26333769, 27436767, 24928908, 30763027, 24668262; Phenotypes: Developmental and epileptic encephalopathy 34 MIM#616645; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 SEC23B Andrew Coventry reviewed gene: SEC23B: Rating: GREEN; Mode of pathogenicity: None; Publications: 19561605, 19621418, 26522472, 27471141, 37373084; Phenotypes: Dyserythropoietic anemia, congenital, type II MIM#224100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 RNASET2 Andrew Coventry reviewed gene: RNASET2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31349848, 19525954, 27091087, 29336640, 18545798, 15851732; Phenotypes: Leukoencephalopathy, cystic, without megalencephaly MIM#612951; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 RNASEH2A Andrew Coventry reviewed gene: RNASEH2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 15870678, 25604658, 23592335, 20301648, 29239743, 16845400, 24183309, 35551623; Phenotypes: Aicardi-Goutieres syndrome 4 MIM#610333, RNASEH2A-related type 1 interferonopathy MONDO:0700259; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 RARB Andrew Coventry reviewed gene: RARB: Rating: AMBER; Mode of pathogenicity: None; Publications: 30880327, 30281527, 24075189, 27120018, 25457163, 17506106; Phenotypes: Microphthalmia, syndromic 12 MIM#615524; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 RAB23 Andrew Coventry reviewed gene: RAB23: Rating: GREEN; Mode of pathogenicity: None; Publications: 17503333, 21412941, 23599695, 25168863; Phenotypes: Carpenter syndrome MIM#201000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PUS7 Andrew Coventry reviewed gene: PUS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 30526862, 30778726, 31583274, 35144859; Phenotypes: Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature MIM#618342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PPIB Andrew Coventry reviewed gene: PPIB: Rating: GREEN; Mode of pathogenicity: None; Publications: 19781681, 32392875; Phenotypes: Osteogenesis imperfecta, type IX MIM#259440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2462 SIRT6 Achchuthan Shanmugasundram gene: SIRT6 was added
gene: SIRT6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SIRT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIRT6 were set to 29555651; 30135584
Review for gene: SIRT6 was set to GREEN
Added comment: PMID:29555651 reported a family with four consecutive cases of late foetal loss with gestational ages between 17 and 35 weeks. The foetuses showed prenatal abnormalities including intrauterine growth restriction (IUGR), microcephaly, craniofacial anomalies, sex reversal in male foetuses, and congenital heart defects. A homozygous inactivating variant in SIRT6 gene (c.187G > C; p.(Asp63His)) was identified by WES in the four foetuses. There is also functional data available from in vitro studies, SIRT6 D63H mouse embryonic stem cells and human induced pluripotent stem cells (iPSCs) derived from D63H homozygous foetuses.

There is also functional evidence available from several other studies including PMID:30135584, where CRISPR-Cas9-based approach was used to generate a SIRT6-null cynomolgus monkey (Macaca fascicularis) model. SIRT6-deficient monkeys died hours after birth and exhibited severe prenatal developmental retardation.

This gene has not been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Prepair 1000+ v1.1868 OPA1 Cassandra Muller reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25012220; Phenotypes: Behr syndrome, 210000 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PDP1 Karina Sandoval reviewed gene: PDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15855260, 31392110, 19184109; Phenotypes: Pyruvate dehydrogenase phosphatase deficiency,MIM#608782; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 NUBPL Cassandra Muller changed review comment from: Well established gene-disease association. Severe, mitochondrial condition with variable severity and progression.; to: Well established gene-disease association. Severe, multi system, mitochondrial condition with variable severity and progression.
Prepair 1000+ v1.1868 NUBPL Cassandra Muller changed review comment from: Well established gene-disease association. Severe, mitochondrial condition with variable severity and progression. Onset in infancy or childhood.; to: Well established gene-disease association. Severe, mitochondrial condition with variable severity and progression.
Prepair 1000+ v1.1868 NUBPL Cassandra Muller reviewed gene: NUBPL: Rating: GREEN; Mode of pathogenicity: None; Publications: 20818383, 32518176, 23553477, 31917109, 32518176, 31787496, 30897263, 22826544; Phenotypes: Mitochondrial complex I deficiency, nuclear type 21, 618242 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 NR2E3 Cassandra Muller Deleted their review
Prepair 1000+ v1.1868 NR2E3 Cassandra Muller reviewed gene: NR2E3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PCSK1 Karina Sandoval reviewed gene: PCSK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14617756, 17595246, 27187081, 27288825, 23562752; Phenotypes: Endocrinopathy due to proprotein convertase 1/3 deficiency,MIM#600955; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 NDUFS4 Cassandra Muller reviewed gene: NDUFS4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 1, 252010 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PCSK1 Karina Sandoval Deleted their review
Prepair 1000+ v1.1868 PCSK1 Karina Sandoval changed review comment from: Unsure if severe enough to include in panel.

MM- Tricky - Hyperphagia & obesity but associated metabolic problems can be severe includeing cases of death in childhood.

PMID:27187081 - some patients displayed morbid obesity and severe hyperphagia, other subjects were only moderately obese. BMI rises from 2 years and patients became obese from early childhood. However, the extreme obesity of the index case at 3 years of age has not been reported in any subsequent patients. Presentation is severe malabsorptive diarrhea, becoming clinically evident within the first 3 months of life. This can be so severe as to lead to a metabolic acidosis. After the age of 2 years, the severity of the malabsorption appears to spontaneously improve, and many children can discontinue
parenteral feeding.

PMID: 27288825 - Nutrition significantly diminshed beyond 2 years and patients can thrive despite the presence of persistent diarrhea that is lifelong and malabsorption throughout life, and early in life will require intravenous support
that may be tapered off as the child ages.; to: Unsure if severe enough to include in panel.

MM- Tricky - Hyperphagia & obesity but associated metabolic problems can be severe includeing cases of death in childhood.

PMID:27187081 - some patients displayed morbid obesity and severe hyperphagia, other subjects were only moderately obese. BMI rises from 2 years and patients became obese from early childhood. However, the extreme obesity of the index case at 3 years of age has not been reported in any subsequent patients. Presentation is severe malabsorptive diarrhea, becoming clinically evident within the first 3 months of life. This can be so severe as to lead to a metabolic acidosis. After the age of 2 years, the severity of the malabsorption appears to spontaneously improve, and many children can discontinue
parenteral feeding.

PMID: 27288825 - Nutrition significantly diminshed beyond 2 years and patients can thrive despite the presence of persistent diarrhea that is lifelong and malabsorption throughout life, and early in life will require intravenous support
that may be tapered off as the child ages.
Prepair 1000+ v1.1868 NDE1 Cassandra Muller reviewed gene: NDE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30637988, 21529751, 34562061; Phenotypes: Lissencephaly 4 (with microcephaly), 614019 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult Cardiac SuperPanel v2.9 Bryony Thompson Changed child panels to: Dilated Cardiomyopathy; Short QT syndrome; Atrial Fibrillation; Cardiac conduction disease; Hypertrophic cardiomyopathy_HCM; Arrhythmogenic Cardiomyopathy; Long QT Syndrome; Catecholaminergic Polymorphic Ventricular Tachycardia; Brugada syndrome; Ventricular Fibrillation
Prepair 1000+ v1.1868 MMP2 Cassandra Muller reviewed gene: MMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11431697, 15691365, 17059372, 17400654; Phenotypes: Multicentric osteolysis, nodulosis, and arthropathy, 259600 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2462 RNU2-2P Achchuthan Shanmugasundram reviewed gene: RNU2-2P: Rating: GREEN; Mode of pathogenicity: None; Publications: 40210679; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.1868 PCSK1 Karina Sandoval reviewed gene: PCSK1: Rating: AMBER; Mode of pathogenicity: None; Publications: 14617756, 17595246, 27187081, 27288825; Phenotypes: Endocrinopathy due to proprotein convertase 1/3 deficiency,MIM#600955; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PAH Karina Sandoval reviewed gene: PAH: Rating: GREEN; Mode of pathogenicity: None; Publications: 27604308, 3008810, 31636599, 32141105; Phenotypes: Phenylketonuria,MIM#261600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 OTUD6B Karina Sandoval reviewed gene: OTUD6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28343629, 32924626, 31147255; Phenotypes: Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies,MIM#617452; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 OPN1LW Karina Sandoval reviewed gene: OPN1LW: Rating: RED; Mode of pathogenicity: None; Publications: 25168334, 32860923, 8213841; Phenotypes: Blue cone monochromacy,MIM#303700, Colorblindness, protan,MIM#303900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.1868 MED12 Melanie Marty reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: None; Publications: 33244166, 32174975, 30006928, 27312080; Phenotypes: MED12-related intellectual disability syndrome, MONDO:0100000; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.1868 HYLS1 Melanie Marty reviewed gene: HYLS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15843405, 18648327, 19400947, 19656802, 32509774, 39626953, 26830932; Phenotypes: Hydrolethalus syndrome (MIM#236680), Ciliopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 FHL1 Melanie Marty changed review comment from: The FHL1 gene is associated with a diverse spectrum of X-linked diseases affecting skeletal and cardiac muscle (PMID: 21310615, 40017287).

Well-established gene-disease association. FHL1 encodes 3 alternatively spliced isoforms - FHL1A, FHL1B, FHL1C composed of different LIM domains. FHL1A is predominant in muscle. Pathogenic variants affected isoform expression differently depending on location in alternatively spliced exons. Location of the variant appears to be related to severity of phenotype. Loss of function is the mechanism of disease.

Reducing body myopathy (RBM) PMID: 18179901, 19716112, 18274675, 19181672, 25274776, 34366191 - XLD inheritance with clinical spectrum that includes severe early-onset to later-onset less progressive conditions including X-linked scapuloperoneal muscular dystrophy & X-linked myopathy with postural muscle atrophy. Pathogenic variants mainly located in more proximal exons (3-6). Fhl1 W122S knock-in mouse model has late-onset mild myopathy.

XL-EDMD PMID: 19716112, 20186852, 20301609 - at least 7 families reported with XLD inheritance (female heterozygous carriers were asymptomatic or had mild myopathy and/or cardiomyopathy). EDMD-associated variants are localized in the distal exons (5-8) and associated with reduced function.; to: The FHL1 gene is associated with a diverse spectrum of X-linked diseases affecting skeletal and cardiac muscle (PMID: 21310615, 40017287).

Well-established gene-disease association. FHL1 encodes 3 alternatively spliced isoforms - FHL1A, FHL1B, FHL1C composed of different LIM domains. FHL1A is predominant in muscle. Pathogenic variants affected isoform expression differently depending on location in alternatively spliced exons. Location of the variant appears to be related to severity of phenotype. Loss of function is the mechanism of disease.

Reducing body myopathy (RBM) PMID: 18179901, 19716112, 18274675, 19181672, 25274776, 34366191 - XLD inheritance with clinical spectrum that includes severe early-onset to later-onset less progressive conditions including X-linked scapuloperoneal muscular dystrophy & X-linked myopathy with postural muscle atrophy. Pathogenic variants mainly located in more proximal exons (3-6). Fhl1 W122S knock-in mouse model has late-onset mild myopathy. Female carriers may experience mild proximal muscle weakness or be asymptomatic.

XL-EDMD PMID: 19716112, 20186852, 20301609 - at least 7 families reported with XLD inheritance (female heterozygous carriers were asymptomatic or had mild myopathy and/or cardiomyopathy). EDMD-associated variants are localized in the distal exons (5-8) and associated with reduced function.
Prepair 1000+ v1.1868 FHL1 Melanie Marty reviewed gene: FHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19716112, 20186852, 20301609, 18179901, 25274776, 34366191, 18274675, 19181672, 21310615, 40017287; Phenotypes: Reducing body myopathy MONDO:0019948, X-linked Emery-Dreifuss muscular dystrophy MONDO:0010680; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.2462 ENAM Bryony Thompson Added comment: Comment on mode of inheritance: Same mechanism of disease for monoallelic vs biallelic. Biallelic phenotype is more severe
Mendeliome v1.2462 ENAM Bryony Thompson Mode of inheritance for gene: ENAM was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Osteogenesis Imperfecta and Osteoporosis v1.3 EMILIN1 Bryony Thompson Marked gene: EMILIN1 as ready
Osteogenesis Imperfecta and Osteoporosis v1.3 EMILIN1 Bryony Thompson Gene: emilin1 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v1.3 EMILIN1 Bryony Thompson Phenotypes for gene: EMILIN1 were changed from arterial tortuosity-bone fragility syndrome to arterial tortuosity-bone fragility syndrome MONDO:0971179
Osteogenesis Imperfecta and Osteoporosis v1.2 EMILIN1 Bryony Thompson Classified gene: EMILIN1 as Green List (high evidence)
Osteogenesis Imperfecta and Osteoporosis v1.2 EMILIN1 Bryony Thompson Gene: emilin1 has been classified as Green List (High Evidence).
Osteogenesis Imperfecta and Osteoporosis v1.1 EMILIN1 Bryony Thompson gene: EMILIN1 was added
gene: EMILIN1 was added to Osteogenesis Imperfecta and Osteoporosis. Sources: Literature
Mode of inheritance for gene: EMILIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EMILIN1 were set to 36351433
Phenotypes for gene: EMILIN1 were set to arterial tortuosity-bone fragility syndrome
Review for gene: EMILIN1 was set to GREEN
gene: EMILIN1 was marked as current diagnostic
Added comment: Prenatal and neonatal fractures are a feature of the condition.
Sources: Literature
Macular Dystrophy/Stargardt Disease v0.54 ELOVL4 Bryony Thompson Mode of inheritance for gene: ELOVL4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Macular Dystrophy/Stargardt Disease v0.53 ELOVL4 Bryony Thompson reviewed gene: ELOVL4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 11138005, 15028284, 11726641, 17208947; Phenotypes: Stargardt disease MONDO:0019353; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Syndromic Retinopathy v0.222 ELOVL4 Bryony Thompson Marked gene: ELOVL4 as ready
Syndromic Retinopathy v0.222 ELOVL4 Bryony Thompson Gene: elovl4 has been classified as Red List (Low Evidence).
Syndromic Retinopathy v0.222 ELOVL4 Bryony Thompson Classified gene: ELOVL4 as Red List (low evidence)
Syndromic Retinopathy v0.222 ELOVL4 Bryony Thompson Gene: elovl4 has been classified as Red List (Low Evidence).
Syndromic Retinopathy v0.221 ELOVL4 Bryony Thompson changed review comment from: Well-established gene-disease associations. Monoallelic loss-of-function variants are associated with macular dystrophy/Stargardt disease. Biallelic loss-of-function variants cause congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome. Monoallelic missense variants cause spinocerebellar ataxia.; to: The macular dystrophy/Stargardt disease phenotype is nonsyndromic and the biallelic congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome doesn't include any retinal findings. Parents who were heterozygous for the variants did not have macular dystrophy.
Syndromic Retinopathy v0.221 ELOVL4 Bryony Thompson edited their review of gene: ELOVL4: Changed rating: RED; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2461 ELOVL4 Bryony Thompson changed review comment from: Well-established gene-disease associations. Monoallelic loss-of-function variants are associated with macular dystrophy/Stargardt disease. Biallelic loss-of-function variants cause congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome. Monoallelic missense variants cause spinocerebellar ataxia.; to: Well-established gene-disease associations. Monoallelic truncating variants in the last exon with an expected dominant effect are associated with macular dystrophy/Stargardt disease. Biallelic loss-of-function variants cause congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome. Monoallelic missense variants cause spinocerebellar ataxia.
Mendeliome v1.2461 ELOVL1 Bryony Thompson Publications for gene: ELOVL1 were set to
Mendeliome v1.2460 ELOVL1 Bryony Thompson Mode of inheritance for gene: ELOVL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2459 ELOVL1 Bryony Thompson reviewed gene: ELOVL1: Rating: RED; Mode of pathogenicity: None; Publications: 35379526; Phenotypes: ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facial features MONDO:0032798; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2459 ELOVL1 Bryony Thompson Deleted their review
Mendeliome v1.2459 EIF2AK4 Bryony Thompson Publications for gene: EIF2AK4 were set to
Mendeliome v1.2458 EIF2AK2 Bryony Thompson Phenotypes for gene: EIF2AK2 were changed from Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness; Dystonia to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness; Dystonia; complex neurodevelopmental disorder MONDO:0100038
Mendeliome v1.2457 EIF2A Bryony Thompson Phenotypes for gene: EIF2A were changed from Intellectual disability, epilepsy to Intellectual disability, epilepsy; MONDO:0700092
Mendeliome v1.2456 EIF2AK1 Bryony Thompson Phenotypes for gene: EIF2AK1 were changed from Intellectual disability; white matter abnormalities to Intellectual disability; white matter abnormalities; MONDO:0100038
Mendeliome v1.2455 EGR2 Bryony Thompson Mode of inheritance for gene: EGR2 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2454 EGR2 Bryony Thompson Mode of inheritance for gene: EGR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v1.321 EFNA4 Bryony Thompson Publications for gene: EFNA4 were set to 29215649; 29168297; 16540516
Fetal anomalies v1.320 EFNA4 Bryony Thompson Classified gene: EFNA4 as Red List (low evidence)
Fetal anomalies v1.320 EFNA4 Bryony Thompson Gene: efna4 has been classified as Red List (Low Evidence).
Fetal anomalies v1.319 EFNA4 Bryony Thompson reviewed gene: EFNA4: Rating: RED; Mode of pathogenicity: None; Publications: 16540516, 19201948, 19772933, 23983218, 29168297, 29215649, 33065355, 34586326, 36140816; Phenotypes: craniosynostosis MONDO:0015469; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Craniosynostosis v1.69 EFNA4 Bryony Thompson Classified gene: EFNA4 as Red List (low evidence)
Craniosynostosis v1.69 EFNA4 Bryony Thompson Gene: efna4 has been classified as Red List (Low Evidence).
Craniosynostosis v1.68 EFNA4 Bryony Thompson reviewed gene: EFNA4: Rating: RED; Mode of pathogenicity: None; Publications: 16540516, 19201948, 19772933, 23983218, 29168297, 29215649, 33065355, 34586326, 36140816; Phenotypes: craniosynostosis MONDO:0015469; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2453 EFNA4 Bryony Thompson Classified gene: EFNA4 as Red List (low evidence)
Mendeliome v1.2453 EFNA4 Bryony Thompson Gene: efna4 has been classified as Red List (Low Evidence).
Mendeliome v1.2452 EFNA4 Bryony Thompson changed review comment from: Supporting animal models, but no compelling evidence in human cases. There’s no supporting segregation evidence and most of the variants reports to date are more common than expected for a dominant disease.

PMID: 34586326 - 3 missense variants identified in a cohort of 101 children with non-syndromic craniosynostosis (EFNA4, c.178C>T: p.His60Tyr - 361 hets & 2 homs in gnomAD v2.1, c.283A>G: p.Lys95Glu, c.349C>A: Pro117Thr - 337 hets in gnomAD v2.1). All 3 variants were present in at least one non-affected family member

PMID: 23983218, 33065355 - Efna4 KO mouse line demonstrates skeletal variance. Homozygous Epha4 null mice had substantially less trabecular bone in femur and vertebra compared to wild-type controls

PMID: 29215649 - 1 missense variant (c.211G>A, p.(Glu71Lys) - 7 hets in gnomAD v2.1) identified in a unicoronal craniosynostosis case in a cohort of 309 craniosynostosis cases

PMID: 29168297 - 1 missense variant (c.550C>T; p.(Leu184Phe) - 1 het in gnomAD v2.1) in a metopic craniosynostosis case from a cohort of 391 single suture craniosynostosis cases. The variant was inherited from an unaffected parent.

PMID: 19772933 - a de novo 1.4 Mb microdeletion of chromosome 1q21.3, including EFNA1, EFNA3 and EFNA4, was identified in a child with moderate mental retardation, microcephaly, arching eyebrows, low set ears, long eyelashes, persistent fetal pads and clinodactyly.

PMID: 19201948 - EphA4 -/- mutant mice exhibit defects in the coronal suture and neural crest-mesoderm boundary that phenocopy those of Twist1+/- mice. The EphA4 +/- mice were similar to the wild-type controls.

PMID: 16540516 - 3 variants (178C>T p.His60Tyr - 361 hets & 2 homs in gnomAD v2.1; c.349C>A p.Pro117Thr - 337 hets in gnomAD v2.1; frameshift 471_472delCCinsA) in cohort of 81 non-syndromic coronal synostosis cases. 2 of the variants were inherited from unaffected parents and Pro117Thr was de novo (confirmed). In vitro functional assays demonstrated partial or complete loss of function for the missense variants. Fibroblasts from the patient with the frameshift expressed in an alternatively spliced minor isoform of EFNA4.; to: Supporting animal models, but no compelling evidence in human cases has been reported since 2006. There’s no supporting segregation evidence and most of the variants reports to date are more common than expected for a dominant disease.

PMID: 34586326 - 3 missense variants identified in a cohort of 101 children with non-syndromic craniosynostosis (EFNA4, c.178C>T: p.His60Tyr - 361 hets & 2 homs in gnomAD v2.1, c.283A>G: p.Lys95Glu, c.349C>A: Pro117Thr - 337 hets in gnomAD v2.1). All 3 variants were present in at least one non-affected family member

PMID: 23983218, 33065355 - Efna4 KO mouse line demonstrates skeletal variance. Homozygous Epha4 null mice had substantially less trabecular bone in femur and vertebra compared to wild-type controls

PMID: 29215649 - 1 missense variant (c.211G>A, p.(Glu71Lys) - 7 hets in gnomAD v2.1) identified in a unicoronal craniosynostosis case in a cohort of 309 craniosynostosis cases

PMID: 29168297 - 1 missense variant (c.550C>T; p.(Leu184Phe) - 1 het in gnomAD v2.1) in a metopic craniosynostosis case from a cohort of 391 single suture craniosynostosis cases. The variant was inherited from an unaffected parent.

PMID: 19772933 - a de novo 1.4 Mb microdeletion of chromosome 1q21.3, including EFNA1, EFNA3 and EFNA4, was identified in a child with moderate mental retardation, microcephaly, arching eyebrows, low set ears, long eyelashes, persistent fetal pads and clinodactyly.

PMID: 19201948 - EphA4 -/- mutant mice exhibit defects in the coronal suture and neural crest-mesoderm boundary that phenocopy those of Twist1+/- mice. The EphA4 +/- mice were similar to the wild-type controls.

PMID: 16540516 - 3 variants (178C>T p.His60Tyr - 361 hets & 2 homs in gnomAD v2.1; c.349C>A p.Pro117Thr - 337 hets in gnomAD v2.1; frameshift 471_472delCCinsA) in cohort of 81 non-syndromic coronal synostosis cases. 2 of the variants were inherited from unaffected parents and Pro117Thr was de novo (confirmed). In vitro functional assays demonstrated partial or complete loss of function for the missense variants. Fibroblasts from the patient with the frameshift expressed in an alternatively spliced minor isoform of EFNA4.
Mendeliome v1.2452 EFNA4 Bryony Thompson edited their review of gene: EFNA4: Changed rating: RED; Changed publications: 16540516, 19201948, 19772933, 23983218, 29168297, 29215649, 33065355, 34586326, 36140816
Macular Dystrophy/Stargardt Disease v0.53 EFEMP1 Bryony Thompson Marked gene: EFEMP1 as ready
Macular Dystrophy/Stargardt Disease v0.53 EFEMP1 Bryony Thompson Gene: efemp1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.53 EFEMP1 Bryony Thompson Added comment: Comment on phenotypes: Singe missense variant (p.Arg345Trp) associated with disease
Macular Dystrophy/Stargardt Disease v0.53 EFEMP1 Bryony Thompson Phenotypes for gene: EFEMP1 were changed from Inherited macular dystrophy (Doyne/dominant drusen) to Doyne honeycomb retinal dystrophy MONDO:0007471
Macular Dystrophy/Stargardt Disease v0.52 EFEMP1 Bryony Thompson Publications for gene: EFEMP1 were set to
Mendeliome v1.2452 EFEMP1 Bryony Thompson Publications for gene: EFEMP1 were set to 32006683; 31792352; 33807164
Intellectual disability syndromic and non-syndromic v1.102 EEF1D Bryony Thompson Classified gene: EEF1D as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.102 EEF1D Bryony Thompson Gene: eef1d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.101 EEF1D Bryony Thompson Publications for gene: EEF1D were set to 30787422; 28097321
Mendeliome v1.2451 EEF1D Bryony Thompson Publications for gene: EEF1D were set to 30787422; 28097321
Intellectual disability syndromic and non-syndromic v1.100 EEF1D Bryony Thompson reviewed gene: EEF1D: Rating: GREEN; Mode of pathogenicity: None; Publications: 38083972, 36576126, 30787422, 28097321; Phenotypes: Neurodevelopmental disorder MONDO:0700092, EEF1D-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2450 EEF1D Bryony Thompson Classified gene: EEF1D as Green List (high evidence)
Mendeliome v1.2450 EEF1D Bryony Thompson Gene: eef1d has been classified as Green List (High Evidence).
Mendeliome v1.2449 EEF1D Bryony Thompson reviewed gene: EEF1D: Rating: GREEN; Mode of pathogenicity: None; Publications: 38083972, 36576126, 30787422, 28097321; Phenotypes: Neurodevelopmental disorder MONDO:0700092, EEF1D-related; Mode of inheritance: None
Deafness_IsolatedAndComplex v1.214 EDN3 Bryony Thompson Added comment: Comment on mode of inheritance: AD association is limited/disputed
Deafness_IsolatedAndComplex v1.214 EDN3 Bryony Thompson Mode of inheritance for gene: EDN3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hirschsprung disease v0.26 EDN3 Bryony Thompson Added comment: Comment on mode of inheritance: AD association is limited/disputed
Hirschsprung disease v0.26 EDN3 Bryony Thompson Mode of inheritance for gene: EDN3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Gastrointestinal neuromuscular disease v1.25 EDN3 Bryony Thompson Added comment: Comment on mode of inheritance: AD association is limited/disputed
Gastrointestinal neuromuscular disease v1.25 EDN3 Bryony Thompson Mode of inheritance for gene: EDN3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Deafness_Isolated v1.70 EDN3 Bryony Thompson Mode of inheritance for gene: EDN3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2449 EDARADD Bryony Thompson Publications for gene: EDARADD were set to
Prepair 1000+ v1.1868 MFN2 Melanie Marty reviewed gene: MFN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15064763, 15549395, 16437557, 20008656; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2A2B, MIM# 617087, Lipomatosis, multiple symmetric, with or without peripheral neuropathy, MIM# 151800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PDE6B Melanie Marty reviewed gene: PDE6B: Rating: RED; Mode of pathogenicity: None; Publications: 8394174, 8075643, 17044014, 7599633, 18854872, 33673512; Phenotypes: Retinitis pigmentosa-40, MIM#613801; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 SCN9A Melanie Marty reviewed gene: SCN9A: Rating: GREEN; Mode of pathogenicity: None; Publications: 18060017; Phenotypes: Insensitivity to pain, congenital, MIM# 243000, Neuropathy, hereditary sensory and autonomic, type IID, MIM# 243000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Predominantly Antibody Deficiency v1.1 BLK Bryony Thompson Marked gene: BLK as ready
Predominantly Antibody Deficiency v1.1 BLK Bryony Thompson Gene: blk has been classified as Red List (Low Evidence).
Predominantly Antibody Deficiency v1.1 BLK Bryony Thompson gene: BLK was added
gene: BLK was added to Predominantly Antibody Deficiency. Sources: Literature
Mode of inheritance for gene: BLK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BLK were set to 25926555
Phenotypes for gene: BLK were set to Common variable immunodeficiency, MONDO:0015517
Review for gene: BLK was set to RED
Added comment: Two individuals in a single family heterozygous for a missense variant p.L3P (46 hets in gnomAD v4) reported with CVID. There have been no other reports in the last 10 years. In vitro functional assays of the variant.
Sources: Literature
Mendeliome v1.2448 BLK Bryony Thompson Classified gene: BLK as Red List (low evidence)
Mendeliome v1.2448 BLK Bryony Thompson Added comment: Comment on list classification: Two individuals in a single family heterozygous for a missense variant p.L3P (46 hets in gnomAD v4) reported with CVID. There have been no other reports in the last 10 years.
Mendeliome v1.2448 BLK Bryony Thompson Gene: blk has been classified as Red List (Low Evidence).
Prepair 1000+ v1.1868 PNPLA6 Andrew Coventry reviewed gene: PNPLA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 38735647, 25480986, 33818269, 32758583, 30097146; Phenotypes: Boucher-Neuhauser syndrome MIM#215470, Oliver-McFarlane syndrome MIM#275400, Spastic paraplegia 39, autosomal recessive MIM#612020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 PAK3 Andrew Coventry reviewed gene: PAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 9731525, 10946356, 12884430, 17853471, 18523455, 24556213, 25666757, 27753653, 28481730, 28126652; Phenotypes: Intellectual developmental disorder, X-linked 30 MIM#300558; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.1868 NAGA Andrew Coventry reviewed gene: NAGA: Rating: GREEN; Mode of pathogenicity: None; Publications: 11313741, 31468281, 15619430, 8782044; Phenotypes: Schindler disease, type I MIM#609241, Schindler disease, type III MIM#609241; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 SEC23A Melanie Marty changed review comment from: SEC23A is an essential component of coat protein complex II (COPII)-coated vesicles that transport secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex.

Boyadjiev et al 2006 (PMID:16980979): One family was reported with a homozygous missense variant and craniolenticulosutural dysplasia (CLSD), with some functional studies supporting pathogenicity.

Boyadjiev et al 2011 (PMID: 21039434): The same authors as above later reported another individual with similar phenotype with a paternally inherited heterozygous missense variant, this variant has 91 hets in gnomAD and the father was unaffected. They suggest digenic inheritance but found no other variants in 3 candidate genes.

Wang et al 2023 (PMID: 37828500): 2 x compound heterozygous missense variants were identified in a patient with CLSD.

Cisarova et al 2022 (PMID: 34580982) 1 x patient with het missense variant inherited from his affected father. Shown to be de novo in the father.

Minale et al 2024 (PMID: 38275611): 1 x patient with de novo het missense variant

Zebrafish models lend some support to the gene-disease association (PMID:16980979, 16980978)

Summary: 2 reports of AR inheritance, 2 reports of AD inheritance, 1 uncertain; to: SEC23A is an essential component of coat protein complex II (COPII)-coated vesicles that transport secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex.

Boyadjiev et al 2006 (PMID:16980979): One family was reported with a homozygous missense variant and craniolenticulosutural dysplasia (CLSD), with some functional studies supporting pathogenicity.

Boyadjiev et al 2011 (PMID: 21039434): The same authors as above later reported another individual with similar phenotype with a paternally inherited heterozygous missense variant, this variant has 91 hets in gnomAD and the father was unaffected. They suggest digenic inheritance but found no other variants in 3 candidate genes.

Wang et al 2023 (PMID: 37828500): 2 x compound heterozygous missense variants were identified in a patient with CLSD.

Cisarova et al 2022 (PMID: 34580982) 1 x patient with CLSD and a het missense variant inherited from his affected father. Shown to be de novo in the father.

Minale et al 2024 (PMID: 38275611): 1 x patient with CLSD and a de novo het missense variant

Zebrafish models lend some support to the gene-disease association (PMID:16980979, 16980978)

Summary: 2 reports of AR inheritance, 2 reports of AD inheritance, 1 uncertain
Prepair 1000+ v1.1868 SEC23A Melanie Marty edited their review of gene: SEC23A: Changed rating: RED; Changed publications: 16980979, 21039434, 16980978, 27148587, 37828500, 34580982, 38275611
Prepair 1000+ v1.1868 SEC23A Melanie Marty reviewed gene: SEC23A: Rating: AMBER; Mode of pathogenicity: None; Publications: 16980979, 21039434, 16980978, 27148587, 37828500, 34580982, PMID: 38275611; Phenotypes: Craniolenticulosutural dysplasia, MIM#607812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 MUSK Andrew Coventry reviewed gene: MUSK: Rating: GREEN; Mode of pathogenicity: None; Publications: 25537362, 25612909, 8653786, 31750350, 15496425, 19949040, 20371544, 32253145; Phenotypes: Fetal akinesia deformation sequence 1 MIM#208150, Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency MIM#616325; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 MTTP Andrew Coventry reviewed gene: MTTP: Rating: GREEN; Mode of pathogenicity: None; Publications: 17275380, 34078172, 34052173, 33258201; Phenotypes: Abetalipoproteinemia MIM#200100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 MTHFD1 Andrew Coventry reviewed gene: MTHFD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32414565, 19033438; Phenotypes: Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia MIM#617780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 MKS1 Andrew Coventry reviewed gene: MKS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17377820, 24886560, 19776033, 33193692, 27570071, 27377014, 18327255, 24608809; Phenotypes: Bardet-Biedl syndrome 13 MIM#615990, Joubert syndrome 28 MIM#617121, Meckel syndrome 1 MIM#249000, Ciliopathy MONDO:0005308; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 MBTPS2 Andrew Coventry reviewed gene: MBTPS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19361614, 27380894, 34902613, 14708109, 22105905, 24313295, 19689518, 24090718, 21600032; Phenotypes: IFAP syndrome with or without BRESHECK syndrome MIM#308205, Osteogenesis imperfecta, type XIX MIM#301014; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.1868 LYST Andrew Coventry reviewed gene: LYST: Rating: GREEN; Mode of pathogenicity: None; Publications: 8896560, 9215680, 31906877, 9215679, 26499269, 24112114, 28145517; Phenotypes: Chediak-Higashi syndrome MIM#214500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 LRMDA Andrew Coventry reviewed gene: LRMDA: Rating: GREEN; Mode of pathogenicity: None; Publications: 37053367, 23395477, 38555393; Phenotypes: Albinism, oculocutaneous, type VII MIM#615179, MONDO:0014070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 LARS2 Andrew Coventry reviewed gene: LARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29205794, 32423379, 30737337, 26537577, 23541342; Phenotypes: Hydrops, lactic acidosis, and sideroblastic anemia MIM#617021, Perrault syndrome 4 MIM#615300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 KIF7 Andrew Coventry reviewed gene: KIF7: Rating: GREEN; Mode of pathogenicity: None; Publications: 21552264, 36580738, 21633164, 19666503, 30445565, 26648833, 26349186, 26174511, 25714560; Phenotypes: Al-Gazali-Bakalinova syndrome MIM#607131, Hydrolethalus syndrome 2 MIM#614120, Acrocallosal syndrome MIM#200990, Joubert syndrome 12 MIM#200990; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 KIAA1109 Andrew Coventry reviewed gene: KIAA1109: Rating: GREEN; Mode of pathogenicity: None; Publications: 29290337, 30906834, 25558065; Phenotypes: Alkuraya-Kucinskas syndrome MIM#617822; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 KCNV2 Andrew Coventry reviewed gene: KCNV2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16909397, 18235024, 21882291, 15722315, 30820446, 21882291, 23115240; Phenotypes: Inherited retinal dystrophy MONDO:0019118, Retinal cone dystrophy 3B MIM#610356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 INPP5K Andrew Coventry reviewed gene: INPP5K: Rating: GREEN; Mode of pathogenicity: None; Publications: 28190456, 28190459, 28940338, 31630891, 33193651, 33792664; Phenotypes: Muscular dystrophy, congenital, with cataracts and intellectual disability MIM#617404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 IFT172 Andrew Coventry reviewed gene: IFT172: Rating: GREEN; Mode of pathogenicity: None; Publications: 30761183, 26763875, 25168386, 24140113, 25168386; Phenotypes: Bardet-Biedl syndrome 20 MIM#619471, Retinitis pigmentosa 71 MIM#616394, Short-rib thoracic dysplasia 10 with or without polydactyly MIM#615630; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 IBA57 Andrew Coventry reviewed gene: IBA57: Rating: GREEN; Mode of pathogenicity: None; Publications: 23462291, 25971455, 25609768, 28913435, 28671726, 30258207; Phenotypes: Mitochondrial disease MONDO:0044970, Multiple mitochondrial dysfunctions syndrome 3 MIM#615330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 HSPD1 Andrew Coventry reviewed gene: HSPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18571143, 27405012, 32532876, 28377887, 27405012; Phenotypes: Leukodystrophy, hypomyelinating, 4 MIM#612233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 HPS3 Andrew Coventry reviewed gene: HPS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 11455388, 31880485, 31621111, 30990103; Phenotypes: Hermansky-Pudlak syndrome 3 MIM#614072; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 HAMP Andrew Coventry reviewed gene: HAMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 12469120, 12490283, 34828384, 15198949; Phenotypes: Hemochromatosis, type 2B MIM#613313; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 HADH Andrew Coventry reviewed gene: HADH: Rating: GREEN; Mode of pathogenicity: None; Publications: 1835339, 10347277, 10931422; Phenotypes: 3-hydroxyacyl-CoA dehydrogenase deficiency MIM#231530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 GLDN Andrew Coventry reviewed gene: GLDN: Rating: GREEN; Mode of pathogenicity: None; Publications: 27616481, 32812332, 28726266, 35806855; Phenotypes: Lethal congenital contracture syndrome 11 MIM#617194; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 GBA Andrew Coventry reviewed gene: GBA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Gaucher disease, perinatal lethal MIM#608013; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 FTSJ1 Andrew Coventry reviewed gene: FTSJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15342698, 18081026, 15162322, 26310293; Phenotypes: Intellectual developmental disorder, X-linked 9 MIM#309549, X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.1868 FRAS1 Andrew Coventry reviewed gene: FRAS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12766769, 18671281, 16894541, 17163535; Phenotypes: Fraser syndrome 1 MIM#219000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 FKBP14 Andrew Coventry reviewed gene: FKBP14: Rating: GREEN; Mode of pathogenicity: None; Publications: 22265013, 24773188, 27149304, 31132235, 30561154, 28617417; Phenotypes: Ehlers-Danlos syndrome, kyphoscoliotic type, 2 MIM#614557; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 FGD4 Andrew Coventry reviewed gene: FGD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 17564959, 31152969, 28847448, 28543957, 17564972; Phenotypes: Charcot-Marie-Tooth disease, type 4H MIM#609311, Charcot-Marie-Tooth disease MONDO:0015626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 FANCL Andrew Coventry reviewed gene: FANCL: Rating: GREEN; Mode of pathogenicity: None; Publications: 19405097, 25754594, 33394227, 33224012, 12973351, 31513304; Phenotypes: Fanconi anemia, complementation group L MIM#614083; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 FANCD2 Andrew Coventry reviewed gene: FANCD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301575, 17436244, 25703294, 23613520; Phenotypes: Fanconi anemia, complementation group D2 MIM#227646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 FAM20C Andrew Coventry reviewed gene: FAM20C: Rating: GREEN; Mode of pathogenicity: None; Publications: 19250384, 32299476, 20825432, 33676444, 32833257; Phenotypes: Raine syndrome MIM#259775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 EIF2B3 Andrew Coventry reviewed gene: EIF2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 11835386, 19158808, 21484434, 18263758, 25843247, 25761052, 28904586, 28597716; Phenotypes: Leukoencephalopathy with vanishing white matter 3, with or without ovarian failure MIM#620313; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 POLE Andrew Coventry gene: POLE was added
gene: POLE was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: POLE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLE were set to 30503519; 23230001; 25948378; 36071887
Phenotypes for gene: POLE were set to IMAGE-I syndrome MIM#618336; FILS syndrome MIM#615139
Review for gene: POLE was set to GREEN
Added comment: IMAGE-I Syndrome
Autosomal recessive disorder characterised by intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency. Patients exhibit distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency.
Well established gene-disease association. Reported in greater than 10 families.
Note recurrent intronic variant, c.1686+32C-G (intron 15) in IMAGE-I, found in combination with multiple other variants.

FILS syndrome
FILS syndrome is characterised by mild facial dysmorphism, mainly malar hypoplasia, livedo on the skin since birth, immunodeficiency resulting in recurrent infections, and short stature.
PMID: 23230001 - French consanguineoius kindred: 11 affected individuals displayed mild facial dysmorphism, immunodeficiency, livedo, and short stature. 3 additional members displayed two or three of these four features. Homozygous for splicing site variant: c.4444+3A>G.
PMID: 25948378 - Palestinian girl, with same homozygous variant as reported in French family.
PMID: 36071887 - 4y.o. Chinese boy with c.5811 + 2T > C and c.2006G > A variants.
PMID: 32705701 - 6y.o. hispanic boy reported with homozygous c.100C>T(p.Arg34Cys
Total of 14 affected individuals across 4 families.
Sources: Literature
Prepair 1000+ v1.1868 CHMP1A Andrew Coventry gene: CHMP1A was added
gene: CHMP1A was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: CHMP1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP1A were set to 23023333; 37789895
Phenotypes for gene: CHMP1A were set to Pontocerebellar hypoplasia, type 8 MIM#614961
Review for gene: CHMP1A was set to AMBER
Added comment: Pontocerebellar hypoplasia type 8 is an autosomal recessive neurodevelopmental disorder characterised by severe psychomotor impediment, abnormal movements, hypotonia, spasticity, and variable visual defects. Brain MRI shows pontocerebellar hypoplasia, decreased cerebral white matter, and a thin corpus callosum.

Zebrafish model present.
PMID: 23023333 - Three families reported, 2 variants; two families likely with founder effect.
PMID: 37789895 - describe novel variants in an affected individual, one is deletion of exon 1, other is c.53 T > C (p.Leu18Pro).
Total 4 families now reported with 4 variants.
Sources: Literature
Prepair 1000+ v1.1868 POLR1D Andrew Coventry gene: POLR1D was added
gene: POLR1D was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: POLR1D was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POLR1D were set to 21131976; 24603435; 27448281; 25790162
Phenotypes for gene: POLR1D were set to Treacher Collins syndrome 2 MIM#613717
Review for gene: POLR1D was set to AMBER
Added comment: Treacher Collins syndrome is a disorder of craniofacial development characterised by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss.

Currently, only one study reporting AR TCS, 1 pathogenic variant in 4 affected individuals, across 2 unrelated consanguineous families. PMID: 24603435.
Adding gene, requiring further evidence in humans for consideration for inclusion in screening of AR TCS.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.100 SPOUT1 Zornitza Stark Phenotypes for gene: SPOUT1 were changed from complex neurodevelopmental disorder MONDO:0100038, SPOUT1-related to Neurodevelopmental disorder with poor growth, seizures, and brain abnormalities, MIM# 621154
Intellectual disability syndromic and non-syndromic v1.99 SPOUT1 Zornitza Stark reviewed gene: SPOUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with poor growth, seizures, and brain abnormalities, MIM# 621154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.126 SPOUT1 Zornitza Stark Phenotypes for gene: SPOUT1 were changed from complex neurodevelopmental disorder MONDO:0100038, SPOUT1-related to Neurodevelopmental disorder with poor growth, seizures, and brain abnormalities, MIM# 621154
Genetic Epilepsy v1.125 SPOUT1 Zornitza Stark reviewed gene: SPOUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with poor growth, seizures, and brain abnormalities, MIM# 621154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.303 SPOUT1 Zornitza Stark Phenotypes for gene: SPOUT1 were changed from complex neurodevelopmental disorder MONDO:0100038, SPOUT1-related to Neurodevelopmental disorder with poor growth, seizures, and brain abnormalities, MIM# 621154
Microcephaly v1.302 SPOUT1 Zornitza Stark reviewed gene: SPOUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with poor growth, seizures, and brain abnormalities, MIM# 621154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2447 SPOUT1 Zornitza Stark reviewed gene: SPOUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with poor growth, seizures, and brain abnormalities, MIM# 621154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2447 SPOUT1 Zornitza Stark Phenotypes for gene: SPOUT1 were changed from complex neurodevelopmental disorder MONDO:0100038, SPOUT1-related to Neurodevelopmental disorder with poor growth, seizures, and brain abnormalities, MIM# 621154
Fetal anomalies v1.319 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly (MONDO:0016296), DISP1-related to Holoprosencephaly 10, MIM# 621143
Fetal anomalies v1.318 DISP1 Zornitza Stark edited their review of gene: DISP1: Changed phenotypes: Holoprosencephaly 10, MIM# 621143
Intellectual disability syndromic and non-syndromic v1.99 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly (MONDO:0016296), DISP1-related to Holoprosencephaly 10, MIM# 621143
Intellectual disability syndromic and non-syndromic v1.98 DISP1 Zornitza Stark edited their review of gene: DISP1: Changed phenotypes: Holoprosencephaly 10, MIM# 621143
Mendeliome v1.2446 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly, MONDO:0016296 to Holoprosencephaly 10, MIM# 621143
Holoprosencephaly and septo-optic dysplasia v1.18 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly, MONDO:0016296 to Holoprosencephaly 10, MIM# 621143
Hair disorders v0.73 KRT83 Zornitza Stark Phenotypes for gene: KRT83 were changed from Monilethrix, 158000 to Monilethrix, MIM#621170
Hair disorders v0.72 KRT83 Zornitza Stark edited their review of gene: KRT83: Changed phenotypes: Monilethrix , MIM#621170
Mendeliome v1.2445 KRT83 Zornitza Stark Phenotypes for gene: KRT83 were changed from Erythrokeratodermia variabilis et progressiva 5, MIM# 617756; Monilethrix , MIM#158000 to Erythrokeratodermia variabilis et progressiva 5, MIM# 617756; Monilethrix , MIM#621170
Mendeliome v1.2444 KRT83 Zornitza Stark edited their review of gene: KRT83: Changed phenotypes: Erythrokeratodermia variabilis et progressiva 5, MIM# 617756, Monilethrix , MIM#621170
Hair disorders v0.72 KRT81 Zornitza Stark Phenotypes for gene: KRT81 were changed from Monilethrix, MIM# 158000 to Monilethrix, MIM# 621169
Hair disorders v0.71 KRT81 Zornitza Stark edited their review of gene: KRT81: Changed phenotypes: Monilethrix, MIM# 621169
Mendeliome v1.2444 KRT81 Zornitza Stark Phenotypes for gene: KRT81 were changed from Monilethrix, MIM# 158000 to Monilethrix, MIM# 621169
Mendeliome v1.2443 KRT81 Zornitza Stark edited their review of gene: KRT81: Changed phenotypes: Monilethrix, MIM# 621169
Infertility and Recurrent Pregnancy Loss v0.63 ZP3 Zornitza Stark Marked gene: ZP3 as ready
Infertility and Recurrent Pregnancy Loss v0.63 ZP3 Zornitza Stark Gene: zp3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.63 ZP3 Zornitza Stark Classified gene: ZP3 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.63 ZP3 Zornitza Stark Gene: zp3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.62 ZP2 Zornitza Stark Marked gene: ZP2 as ready
Infertility and Recurrent Pregnancy Loss v0.62 ZP2 Zornitza Stark Gene: zp2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.62 ZP2 Zornitza Stark Classified gene: ZP2 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.62 ZP2 Zornitza Stark Gene: zp2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.61 ZP1 Zornitza Stark Marked gene: ZP1 as ready
Infertility and Recurrent Pregnancy Loss v0.61 ZP1 Zornitza Stark Gene: zp1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.61 ZP1 Zornitza Stark Classified gene: ZP1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.61 ZP1 Zornitza Stark Gene: zp1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.60 WNT6 Zornitza Stark Marked gene: WNT6 as ready
Infertility and Recurrent Pregnancy Loss v0.60 WNT6 Zornitza Stark Gene: wnt6 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.60 WNT6 Zornitza Stark Classified gene: WNT6 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v0.60 WNT6 Zornitza Stark Gene: wnt6 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.59 WNT6 Zornitza Stark reviewed gene: WNT6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: recurrent pregnancy loss susceptibility, MONDO:0000144; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v0.59 USP26 Zornitza Stark Marked gene: USP26 as ready
Infertility and Recurrent Pregnancy Loss v0.59 USP26 Zornitza Stark Gene: usp26 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.59 USP26 Zornitza Stark Classified gene: USP26 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v0.59 USP26 Zornitza Stark Gene: usp26 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.58 USP26 Zornitza Stark reviewed gene: USP26: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure, X-linked 6, MIM# 301101; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Infertility and Recurrent Pregnancy Loss v0.58 USP26 Zornitza Stark Classified gene: USP26 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.58 USP26 Zornitza Stark Gene: usp26 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.57 UBE2B Zornitza Stark Marked gene: UBE2B as ready
Infertility and Recurrent Pregnancy Loss v0.57 UBE2B Zornitza Stark Gene: ube2b has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.57 UBE2B Zornitza Stark Classified gene: UBE2B as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.57 UBE2B Zornitza Stark Gene: ube2b has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.56 TUBB8 Zornitza Stark Marked gene: TUBB8 as ready
Infertility and Recurrent Pregnancy Loss v0.56 TUBB8 Zornitza Stark Gene: tubb8 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.56 TUBB8 Zornitza Stark Classified gene: TUBB8 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.56 TUBB8 Zornitza Stark Gene: tubb8 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.55 TACC3 Zornitza Stark Phenotypes for gene: TACC3 were changed from to Female infertility due to oocyte meiotic arrest, MONDO:0044626
Infertility and Recurrent Pregnancy Loss v0.54 TACC3 Zornitza Stark Marked gene: TACC3 as ready
Infertility and Recurrent Pregnancy Loss v0.54 TACC3 Zornitza Stark Gene: tacc3 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.54 TACC3 Zornitza Stark Classified gene: TACC3 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v0.54 TACC3 Zornitza Stark Gene: tacc3 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.53 TACC3 Zornitza Stark reviewed gene: TACC3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Female infertility due to oocyte meiotic arrest, MONDO:0044626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.53 STAG3 Zornitza Stark Marked gene: STAG3 as ready
Infertility and Recurrent Pregnancy Loss v0.53 STAG3 Zornitza Stark Gene: stag3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.53 STAG3 Zornitza Stark Classified gene: STAG3 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.53 STAG3 Zornitza Stark Gene: stag3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.52 STAG3 Zornitza Stark reviewed gene: STAG3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Premature ovarian failure 8, MIM# 615723, Spermatogenic failure 61, MIM# 619672; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.52 SOHLH1 Zornitza Stark Marked gene: SOHLH1 as ready
Infertility and Recurrent Pregnancy Loss v0.52 SOHLH1 Zornitza Stark Gene: sohlh1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.52 SOHLH1 Zornitza Stark Classified gene: SOHLH1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.52 SOHLH1 Zornitza Stark Gene: sohlh1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.51 SLC26A8 Zornitza Stark Marked gene: SLC26A8 as ready
Infertility and Recurrent Pregnancy Loss v0.51 SLC26A8 Zornitza Stark Gene: slc26a8 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.51 SLC26A8 Zornitza Stark Classified gene: SLC26A8 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.51 SLC26A8 Zornitza Stark Gene: slc26a8 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.50 PSMC3IP Zornitza Stark Marked gene: PSMC3IP as ready
Infertility and Recurrent Pregnancy Loss v0.50 PSMC3IP Zornitza Stark Gene: psmc3ip has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.50 PSMC3IP Zornitza Stark Classified gene: PSMC3IP as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.50 PSMC3IP Zornitza Stark Gene: psmc3ip has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.49 PRDM9 Zornitza Stark Marked gene: PRDM9 as ready
Infertility and Recurrent Pregnancy Loss v0.49 PRDM9 Zornitza Stark Gene: prdm9 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.49 PRDM9 Zornitza Stark Classified gene: PRDM9 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.49 PRDM9 Zornitza Stark Gene: prdm9 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.48 POF1B Zornitza Stark Marked gene: POF1B as ready
Infertility and Recurrent Pregnancy Loss v0.48 POF1B Zornitza Stark Gene: pof1b has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.48 POF1B Zornitza Stark edited their review of gene: POF1B: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Infertility and Recurrent Pregnancy Loss v0.48 POF1B Zornitza Stark Classified gene: POF1B as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v0.48 POF1B Zornitza Stark Gene: pof1b has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.47 POF1B Zornitza Stark reviewed gene: POF1B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Premature ovarian failure 2B, MIM# 300604; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.47 PDHA2 Zornitza Stark Marked gene: PDHA2 as ready
Infertility and Recurrent Pregnancy Loss v0.47 PDHA2 Zornitza Stark Gene: pdha2 has been classified as Red List (Low Evidence).
Infertility and Recurrent Pregnancy Loss v0.47 PDHA2 Zornitza Stark Classified gene: PDHA2 as Red List (low evidence)
Infertility and Recurrent Pregnancy Loss v0.47 PDHA2 Zornitza Stark Gene: pdha2 has been classified as Red List (Low Evidence).
Infertility and Recurrent Pregnancy Loss v0.46 PDHA2 Zornitza Stark reviewed gene: PDHA2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 70, MIM# 619828; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.46 PATL2 Zornitza Stark Marked gene: PATL2 as ready
Infertility and Recurrent Pregnancy Loss v0.46 PATL2 Zornitza Stark Gene: patl2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.46 PATL2 Zornitza Stark Classified gene: PATL2 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.46 PATL2 Zornitza Stark Gene: patl2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.45 PADI6 Zornitza Stark Marked gene: PADI6 as ready
Infertility and Recurrent Pregnancy Loss v0.45 PADI6 Zornitza Stark Gene: padi6 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.45 PADI6 Zornitza Stark Classified gene: PADI6 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.45 PADI6 Zornitza Stark Gene: padi6 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.44 NOBOX Zornitza Stark Marked gene: NOBOX as ready
Infertility and Recurrent Pregnancy Loss v0.44 NOBOX Zornitza Stark Gene: nobox has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.44 NOBOX Zornitza Stark Classified gene: NOBOX as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.44 NOBOX Zornitza Stark Gene: nobox has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.43 MSH4 Zornitza Stark Marked gene: MSH4 as ready
Infertility and Recurrent Pregnancy Loss v0.43 MSH4 Zornitza Stark Gene: msh4 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.43 MSH4 Zornitza Stark Classified gene: MSH4 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.43 MSH4 Zornitza Stark Gene: msh4 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.42 FSHR Zornitza Stark Marked gene: FSHR as ready
Infertility and Recurrent Pregnancy Loss v0.42 FSHR Zornitza Stark Gene: fshr has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.42 FSHR Zornitza Stark Classified gene: FSHR as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.42 FSHR Zornitza Stark Gene: fshr has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.41 FSHR Zornitza Stark reviewed gene: FSHR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ovarian dysgenesis 1 MONDO:0024463, Ovarian hyperstimulation syndrome MONDO:0011972; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.41 FSHB Zornitza Stark Marked gene: FSHB as ready
Infertility and Recurrent Pregnancy Loss v0.41 FSHB Zornitza Stark Gene: fshb has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.41 FSHB Zornitza Stark Classified gene: FSHB as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.41 FSHB Zornitza Stark Gene: fshb has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.40 ELL3 Zornitza Stark Marked gene: ELL3 as ready
Infertility and Recurrent Pregnancy Loss v0.40 ELL3 Zornitza Stark Gene: ell3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.40 ELL3 Zornitza Stark Phenotypes for gene: ELL3 were changed from to Pregnancy loss, recurrent, susceptibility to, MONDO:0000144, ELL3-related
Infertility and Recurrent Pregnancy Loss v0.39 ELL3 Zornitza Stark Classified gene: ELL3 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.39 ELL3 Zornitza Stark Gene: ell3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.38 DNAH8 Zornitza Stark Marked gene: DNAH8 as ready
Infertility and Recurrent Pregnancy Loss v0.38 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.38 DNAH8 Zornitza Stark Classified gene: DNAH8 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.38 DNAH8 Zornitza Stark Gene: dnah8 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.37 DNAH1 Zornitza Stark Marked gene: DNAH1 as ready
Infertility and Recurrent Pregnancy Loss v0.37 DNAH1 Zornitza Stark Gene: dnah1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.37 DNAH1 Zornitza Stark Classified gene: DNAH1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.37 DNAH1 Zornitza Stark Gene: dnah1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.36 DHH Zornitza Stark Marked gene: DHH as ready
Infertility and Recurrent Pregnancy Loss v0.36 DHH Zornitza Stark Gene: dhh has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.36 DHH Zornitza Stark Classified gene: DHH as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.36 DHH Zornitza Stark Gene: dhh has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.35 CPEB1 Zornitza Stark Marked gene: CPEB1 as ready
Infertility and Recurrent Pregnancy Loss v0.35 CPEB1 Zornitza Stark Gene: cpeb1 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.35 CPEB1 Zornitza Stark Phenotypes for gene: CPEB1 were changed from Primary ovarian insufficiency, MONDO:0005387 to Primary ovarian insufficiency, MONDO:0005387, CPEB1-related
Infertility and Recurrent Pregnancy Loss v0.34 CPEB1 Zornitza Stark Classified gene: CPEB1 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v0.34 CPEB1 Zornitza Stark Gene: cpeb1 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.33 CPEB1 Zornitza Stark reviewed gene: CPEB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ovarian insufficiency, MONDO:0005387, CPEB1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v0.33 CPEB1 Zornitza Stark Tag SV/CNV tag was added to gene: CPEB1.
Infertility and Recurrent Pregnancy Loss v0.33 CFTR Zornitza Stark Marked gene: CFTR as ready
Infertility and Recurrent Pregnancy Loss v0.33 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.33 CFTR Zornitza Stark Classified gene: CFTR as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.33 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.32 AMHR2 Zornitza Stark Marked gene: AMHR2 as ready
Infertility and Recurrent Pregnancy Loss v0.32 AMHR2 Zornitza Stark Gene: amhr2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.32 AMHR2 Zornitza Stark Classified gene: AMHR2 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.32 AMHR2 Zornitza Stark Gene: amhr2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.31 AMH Zornitza Stark Marked gene: AMH as ready
Infertility and Recurrent Pregnancy Loss v0.31 AMH Zornitza Stark Gene: amh has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.31 AMH Zornitza Stark Classified gene: AMH as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.31 AMH Zornitza Stark Gene: amh has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.30 AARS2 Zornitza Stark Marked gene: AARS2 as ready
Infertility and Recurrent Pregnancy Loss v0.30 AARS2 Zornitza Stark Gene: aars2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.30 AARS2 Zornitza Stark Classified gene: AARS2 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.30 AARS2 Zornitza Stark Gene: aars2 has been classified as Green List (High Evidence).
Arrhythmia_SuperPanel v3.28 Bryony Thompson Panel status changed from promoted to public
Changed child panels to: Short QT syndrome; Atrial Fibrillation; Cardiac conduction disease; Arrhythmogenic Cardiomyopathy; Long QT Syndrome; Catecholaminergic Polymorphic Ventricular Tachycardia; Brugada syndrome; Ventricular Fibrillation
Cardiac conduction disease v1.0 Bryony Thompson promoted panel to version 1.0
Cardiac conduction disease v0.38 Bryony Thompson Panel status changed from internal to public
Cardiac conduction disease v0.36 GNB2 Bryony Thompson Deleted their review
Cardiac conduction disease v0.36 GNB2 Bryony Thompson gene: GNB2 was added
gene: GNB2 was added to Cardiac conduction disease. Sources: Literature
Mode of inheritance for gene: GNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB2 were set to 28219978
Phenotypes for gene: GNB2 were set to Sick sinus syndrome 4, MIM# 619464
Review for gene: GNB2 was set to RED
Added comment: Sources: Literature
Cardiac conduction disease v0.35 GJA5 Bryony Thompson Marked gene: GJA5 as ready
Cardiac conduction disease v0.35 GJA5 Bryony Thompson Gene: gja5 has been classified as Amber List (Moderate Evidence).
Cardiac conduction disease v0.35 GJA5 Bryony Thompson Classified gene: GJA5 as Amber List (moderate evidence)
Cardiac conduction disease v0.35 GJA5 Bryony Thompson Gene: gja5 has been classified as Amber List (Moderate Evidence).
Cardiac conduction disease v0.34 GJA5 Bryony Thompson gene: GJA5 was added
gene: GJA5 was added to Cardiac conduction disease. Sources: NHS GMS
Mode of inheritance for gene: GJA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GJA5 were set to 9501069; 10086977; 22247482; 36352534
Phenotypes for gene: GJA5 were set to heart conduction disease MONDO:0000992
Review for gene: GJA5 was set to AMBER
Added comment: PMID: 9501069, 10086977 - null mouse model with cardiac conduction abnormalities characteristic of first-degree atrioventricular block with associated bundle branch block
PMID: 22247482 - Q58L (absent from gnomAD v4) identified in a proband with progressive familial heart block, segregated to affected sibling and was likely present in mother that died of sudden cardiac death (the variant was absent from the probands father and maternal grandparents, suggesting the variant is de novo in the probands mother but no DNA was available for testing). In vitro functional assays showed the variant (Cx40-Q58L) impairs gap junction formation at cell-cell interfaces.
PMID: 36352534 - a VUS p.(Arg316His) was identified in a case with idiopathic atrioventricular conduction disease. 49 hets in gnomAD v4.
Sources: NHS GMS
Infertility and Recurrent Pregnancy Loss v0.29 UBE2B Jasmine Chew changed review comment from: i) PMID: 23378580 (2013)- Identified nine splicing, four missense and two nonsense alterations in unrelated oligospermic patients, majority are heterozygous, only 3 were homozygous. Their findings suggested that two distinct molecular mechanisms, mRNA editing and splicing processing, were disrupted in oligozoospermia.

ii) PMID: 26223869 (2015): reported four known and novel heterozygous variants in idiopathic azoospermia (IA) patient in the Chinese pop, and one of the missense variant was demonstrated to inhibit the transcriptional regulation activity of SP1 transcription factor, suggesting that it confers a high risk for IA.

iii) PMID: 12784252 (2003)- Ube2b(-/-) mice were shown to present male infertility and their sperm head shape anomalies suggested that Ube2b may be involved in the replacement of nuclear proteins during spermatid chromatin condensation.
Sources: Literature; to: i) PMID: 23378580 (2013)- Identified nine splicing, four missense and two nonsense alterations in unrelated oligospermic patients, majority are heterozygous, only 3 were homozygous. Their findings suggested that two distinct molecular mechanisms, mRNA editing and splicing processing, were disrupted in oligozoospermia.

ii) PMID: 26223869 (2015): Reported four known and novel heterozygous variants in idiopathic azoospermia (IA) patients in the Chinese population, and one of the missense variant was demonstrated to inhibit the transcriptional regulation activity of SP1 transcription factor, suggesting that it confers a high risk for IA.

iii) PMID: 12784252 (2003)- Ube2b(-/-) mice were shown to present male infertility and their sperm head shape anomalies suggested that Ube2b may be involved in the replacement of nuclear proteins during spermatid chromatin condensation.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 UBE2B Jasmine Chew edited their review of gene: UBE2B: Changed rating: GREEN
Infertility and Recurrent Pregnancy Loss v0.29 UBE2B Jasmine Chew changed review comment from: i) PMID: 23378580 (2013)- identified nine splicing, four missense and two nonsense alterations in unrelated oligospermic patients, majority are heterozygous, only 3 were homozygous.

ii) PMID: 26223869 (2015): reported four known and novel heterozygous variants in idiopathic azoospermia (IA) patient in the Chinese pop, and one of the missense variant was demonstrated to inhibit the transcriptional regulation activity of SP1 transcription factor, suggesting that it confers a high risk for IA.

iii) PMID: 12784252 (2003)- Ube2b(-/-) mice were shown to present male infertility and their sperm head shape anomalies suggested that Ube2b may be involved in the replacement of nuclear proteins during spermatid chromatin condensation.
Sources: Literature; to: i) PMID: 23378580 (2013)- Identified nine splicing, four missense and two nonsense alterations in unrelated oligospermic patients, majority are heterozygous, only 3 were homozygous. Their findings suggested that two distinct molecular mechanisms, mRNA editing and splicing processing, were disrupted in oligozoospermia.

ii) PMID: 26223869 (2015): reported four known and novel heterozygous variants in idiopathic azoospermia (IA) patient in the Chinese pop, and one of the missense variant was demonstrated to inhibit the transcriptional regulation activity of SP1 transcription factor, suggesting that it confers a high risk for IA.

iii) PMID: 12784252 (2003)- Ube2b(-/-) mice were shown to present male infertility and their sperm head shape anomalies suggested that Ube2b may be involved in the replacement of nuclear proteins during spermatid chromatin condensation.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 UBE2B Jasmine Chew gene: UBE2B was added
gene: UBE2B was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: UBE2B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: UBE2B were set to 23378580; 26223869; 12784252
Phenotypes for gene: UBE2B were set to Male infertility, MONDO:0005372
Added comment: i) PMID: 23378580 (2013)- identified nine splicing, four missense and two nonsense alterations in unrelated oligospermic patients, majority are heterozygous, only 3 were homozygous.

ii) PMID: 26223869 (2015): reported four known and novel heterozygous variants in idiopathic azoospermia (IA) patient in the Chinese pop, and one of the missense variant was demonstrated to inhibit the transcriptional regulation activity of SP1 transcription factor, suggesting that it confers a high risk for IA.

iii) PMID: 12784252 (2003)- Ube2b(-/-) mice were shown to present male infertility and their sperm head shape anomalies suggested that Ube2b may be involved in the replacement of nuclear proteins during spermatid chromatin condensation.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 DNAH8 Jasmine Chew gene: DNAH8 was added
gene: DNAH8 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: DNAH8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH8 were set to 32619401; 32681648; 36308074; 33704367
Phenotypes for gene: DNAH8 were set to Spermatogenic failure 46, MIM# 619095
Review for gene: DNAH8 was set to GREEN
Added comment: Literature in OMIM- PMID: 32619401;32681648- multiple cases with multiple morphologic abnormalities of the sperm flagella (MMAF) carrying biallelic variants

New papers:
i) PMID: 36308074- A novel homozygous frameshift variant in DNAH8 causes MMAF in a consanguineous Pakistani family. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 variant. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Immunofluorescence assay also showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa.

ii) PMID: 33704367- Two unrelated infertile Chinese patients with MMAF carrying different compound heterozygous variants. Immunofluorescence assay showed that DNAH8 protein expression was significantly decreased in the sperm tail of the patients, and electron microscopy exhibited an abnormal flagellum ultrastructure, while clinical pregnancy could be achieved by intracytoplasmic sperm injection.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 DNAH1 Jasmine Chew changed review comment from: Literature in OMIM- PMID: 24360805, 27798045, 27573432, 28552195, 28577616, 29449551- multiple unrelated cases with multiple morphological abnormalities of the sperm flagella (MMAF)
Sources: Literature; to: Literature in OMIM- PMID: 24360805, 27798045, 27573432, 28552195, 28577616, 29449551- multiple unrelated cases with multiple morphological abnormalities of the sperm flagella (MMAF) carrying biallelic variants
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 DNAH1 Jasmine Chew gene: DNAH1 was added
gene: DNAH1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: DNAH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH1 were set to 24360805; 27798045; 27573432; 28552195; 28577616; 29449551
Phenotypes for gene: DNAH1 were set to Spermatogenic failure 18 , MIM# 617576
Review for gene: DNAH1 was set to GREEN
Added comment: Literature in OMIM- PMID: 24360805, 27798045, 27573432, 28552195, 28577616, 29449551- multiple unrelated cases with multiple morphological abnormalities of the sperm flagella (MMAF)
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 DHH Jasmine Chew gene: DHH was added
gene: DHH was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: DHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHH were set to 25927242; 28589169; 28708305; 29471294; 40176231
Phenotypes for gene: DHH were set to 46XY gonadal dysgenesis with minifascicular neuropathy, MIM# 607080
Review for gene: DHH was set to GREEN
Added comment: Literature in OMIM- PubMed: 25927242; 28589169; 28708305; 29471294- biallelic variants in affected women with primary amenorrhea, also one woman from PMID:29471294 had 2 uneventful pregnancies.

New paper:
PMID: 40176231-novel homozygous missense variant (P. Ser185Pro) in an Indian female with primary amenorrhea and severe motor and sensory neuropathy with Charcot's joints.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 CPEB1 Jasmine Chew changed review comment from: i) PMID: 32354341 (2020)- heterozygous deletion of exons 8-12 in a Chinese patient with primary amenorrhea.

ii) PMID: 33095795 (2020)- heterozygous 83.8-kb deletion (in the similar region reported previously) and a heterozygous missense variant (p.R87C) reported in two Brazilian female with POI (POI-4, POI-14).

iii) PMID: 27003306 (2016)- identified three POI patients carrying overlapping microdeletions disrupting CPEB1, which is the only gene known to be involved in reproduction in the deleted regions. Also suggested given that CEPB1 is located in a chromosomal region containing LCRs, the involvement of this gene in POI can be hypothesized to be related to microdeletions in the 15q25.2 region rather than to CPEB1 variants.

iv) PMID: 21256485 (2011)- POF-87 with novel heterozygous microdeletion including CPEB1 (1.67 Mb del including the entire CPEB1).
Sources: Literature; to: i) PMID: 32354341 (2020)- heterozygous deletion of exons 8-12 in a Chinese patient with primary amenorrhea.

ii) PMID: 33095795 (2020)- heterozygous 83.8-kb deletion (in the similar region reported previously) and a heterozygous missense variant (p.R87C) reported in two Brazilian female with POI (POI-4, POI-14).

iii) PMID: 27003306 (2016)- identified three POI patients carrying overlapping microdeletions disrupting CPEB1, which is the only gene known to be involved in reproduction in the deleted regions. Also suggested given that CEPB1 is located in a chromosomal region containing LCRs, the involvement of this gene in POI can be hypothesized to be related to microdeletions in the 15q25.2 region rather than to CPEB1 variants.

iv) PMID: 21256485 (2011)- POF-87 with novel heterozygous microdeletion including CPEB1 (1.67 Mb del including the entire CPEB1).

Note: CPEB1 dosage sensitivity curation pending review
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 CPEB1 Jasmine Chew gene: CPEB1 was added
gene: CPEB1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: CPEB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CPEB1 were set to 21256485; 27003306; 33095795; 32354341
Phenotypes for gene: CPEB1 were set to Primary ovarian insufficiency, MONDO:0005387
Review for gene: CPEB1 was set to GREEN
Added comment: i) PMID: 32354341 (2020)- heterozygous deletion of exons 8-12 in a Chinese patient with primary amenorrhea.

ii) PMID: 33095795 (2020)- heterozygous 83.8-kb deletion (in the similar region reported previously) and a heterozygous missense variant (p.R87C) reported in two Brazilian female with POI (POI-4, POI-14).

iii) PMID: 27003306 (2016)- identified three POI patients carrying overlapping microdeletions disrupting CPEB1, which is the only gene known to be involved in reproduction in the deleted regions. Also suggested given that CEPB1 is located in a chromosomal region containing LCRs, the involvement of this gene in POI can be hypothesized to be related to microdeletions in the 15q25.2 region rather than to CPEB1 variants.

iv) PMID: 21256485 (2011)- POF-87 with novel heterozygous microdeletion including CPEB1 (1.67 Mb del including the entire CPEB1).
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 CFTR Jasmine Chew gene: CFTR was added
gene: CFTR was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: CFTR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFTR were set to 30214069; 40169970; 39592508; 39356031
Phenotypes for gene: CFTR were set to Congenital bilateral absence of vas deferens, MIM# 277180
Review for gene: CFTR was set to GREEN
Added comment: OMIM- Found in more than 25% of men with obstructive azoospermia, involving a complete or partial defect of the Wolffian duct derivatives; PMID: 30214069

New case reports- PMID: 40169970; 39592508; 39356031
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 AMHR2 Jasmine Chew gene: AMHR2 was added
gene: AMHR2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: AMHR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMHR2 were set to 7493017; 8872466; 19457927; 35052499; 33025551; 34480531
Phenotypes for gene: AMHR2 were set to Persistent Mullerian duct syndrome, type I, MIM #261550
Review for gene: AMHR2 was set to GREEN
Added comment: Literature in OMIM- PMID: 7493017; 8872466;19457927

New papers:
i) PMID: 35052499- compound heterozygous variants in case 2 and case 3 with azoospermia/oligospermia.

ii) PMID: 33025551- seven different variants identified in 11 cases from six unrelated Turkish families with PMDS (didn't mention if they were infertile).

iii) PMID: 34480531- compound heterozygous variants of c.1387C>T (p.R463C) and c.1219C>T (p.R407X) in exons 9 and 10, respectively, in two brothers who had a history of bilateral cryptorchidism with orchidopexy as well as infertility due to azoospermia.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 AMH Jasmine Chew changed review comment from: Literature in OMIM- PMID: 2023927;1483695;11760020

New papers:
i) PMID: 39889328 - novel homozygous missense p.Pro550Leu in a Tuscinian man with primary infertilitydue to Persistent Müllerian duct syndrome and biopsy revealed no spermatozoa

ii) PMID: 35052499- homozygous 4-bp deletion; c.321_324del:p.Q109Lfs*29 in exon 1 in case 1 with non-obstructive azoospermia, leading to the loss of function of AMH.
; to: Literature in OMIM- PMID: 2023927;1483695;11760020

New papers:
i) PMID: 39889328 - novel homozygous missense p.Pro550Leu in a Tuscinian man with primary infertility due to Persistent Müllerian duct syndrome and biopsy revealed no spermatozoa.

ii) PMID: 35052499- homozygous 4-bp deletion; c.321_324del:p.Q109Lfs*29 in exon 1 in case 1 with non-obstructive azoospermia, leading to the loss of function of AMH.
Infertility and Recurrent Pregnancy Loss v0.29 AMH Jasmine Chew changed review comment from: Literature in OMIM- PMID: 2023927;1483695;11760020

New papers:
i) PMID: 39889328 - novel homozygous missense p.Pro550Leu in a Tuscinian man with primary infertilitydue to Persistent Müllerian duct syndrome and biopsy revealed no spermatozoa

ii) PMID: 35052499- case 1 with non-obstructive azoospermia carrying homozygous 4-bp deletion; c.321_324del:p.Q109Lfs*29 in exon 1 of AMH, leading to the loss of function of AMH.
Sources: Literature; to: Literature in OMIM- PMID: 2023927;1483695;11760020

New papers:
i) PMID: 39889328 - novel homozygous missense p.Pro550Leu in a Tuscinian man with primary infertilitydue to Persistent Müllerian duct syndrome and biopsy revealed no spermatozoa

ii) PMID: 35052499- homozygous 4-bp deletion; c.321_324del:p.Q109Lfs*29 in exon 1 in case 1 with non-obstructive azoospermia, leading to the loss of function of AMH.
Infertility and Recurrent Pregnancy Loss v0.29 AMH Jasmine Chew gene: AMH was added
gene: AMH was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: AMH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMH were set to 2023927; 1483695; 11760020; 39889328; 35052499
Phenotypes for gene: AMH were set to Persistent Mullerian duct syndrome, type I, MIM# 261550
Review for gene: AMH was set to GREEN
Added comment: Literature in OMIM- PMID: 2023927;1483695;11760020

New papers:
i) PMID: 39889328 - novel homozygous missense p.Pro550Leu in a Tuscinian man with primary infertilitydue to Persistent Müllerian duct syndrome and biopsy revealed no spermatozoa

ii) PMID: 35052499- case 1 with non-obstructive azoospermia carrying homozygous 4-bp deletion; c.321_324del:p.Q109Lfs*29 in exon 1 of AMH, leading to the loss of function of AMH.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 AARS2 Jasmine Chew edited their review of gene: AARS2: Changed phenotypes: Progressive leukoencephalopathy with ovarian failure, MIM# 615889
Infertility and Recurrent Pregnancy Loss v0.29 AARS2 Jasmine Chew gene: AARS2 was added
gene: AARS2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: AARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS2 were set to 24808023; 32775515; 31280959; 29749055
Phenotypes for gene: AARS2 were set to Leukoencephalopathy, progressive, with ovarian failure, MIM# 615889
Review for gene: AARS2 was set to GREEN
Added comment: Literature in OMIM- PMID:24808023- compound heterozygous missense variants in 5 women with premature ovarian failure among 6 with progressive leukoencephalopathy, and studies of the yeast homologs of 2 variants (F50C and R521X) showed that they resulted in a complete or partial loss of protein function.

New papers- case reports of biallelic variants in patients with POIPOF
- PMID:32775515; 31280959; 29749055
Sources: Literature
Prepair 1000+ v1.1868 NUP107 Karina Sandoval reviewed gene: NUP107: Rating: GREEN; Mode of pathogenicity: None; Publications: 28280135, 28117080, 30179222, 25558065, 26411495; Phenotypes: Galloway-Mowat syndrome 7, MIM#618348, Nephrotic syndrome, type 11, MIM#616730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 NR0B1 Karina Sandoval reviewed gene: NR0B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19508677, 26030781; Phenotypes: Adrenal hypoplasia, congenital, MIM#300200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.1868 NDUFV2 Karina Sandoval reviewed gene: NDUFV2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33811136, 34405929, 12754703, 26008862, 30770271, 19167255; Phenotypes: Mitochondrial complex I deficiency, nuclear type 7, MIM#618229, MONDO:0044970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 MAPKBP1 Karina Sandoval reviewed gene: MAPKBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28089251, 33623699, 32505465, 32055034; Phenotypes: Nephronophthisis 20, MIM# 617271, MONDO:0014997; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v1.125 ATP11A Bryony Thompson Marked gene: ATP11A as ready
Genetic Epilepsy v1.125 ATP11A Bryony Thompson Gene: atp11a has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.125 ATP11A Bryony Thompson Classified gene: ATP11A as Amber List (moderate evidence)
Genetic Epilepsy v1.125 ATP11A Bryony Thompson Gene: atp11a has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.320 ATP11A Bryony Thompson Publications for gene: ATP11A were set to PMID: 34403372
Leukodystrophy - paediatric v0.319 ATP11A Bryony Thompson Classified gene: ATP11A as Green List (high evidence)
Leukodystrophy - paediatric v0.319 ATP11A Bryony Thompson Gene: atp11a has been classified as Green List (High Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.134 TRPM4 Bryony Thompson Publications for gene: TRPM4 were set to 30528822
Palmoplantar Keratoderma and Erythrokeratoderma v0.133 TRPM4 Bryony Thompson Classified gene: TRPM4 as Amber List (moderate evidence)
Palmoplantar Keratoderma and Erythrokeratoderma v0.133 TRPM4 Bryony Thompson Gene: trpm4 has been classified as Amber List (Moderate Evidence).
Palmoplantar Keratoderma and Erythrokeratoderma v0.132 TRPM4 Bryony Thompson reviewed gene: TRPM4: Rating: AMBER; Mode of pathogenicity: Other; Publications: 30528822, 36341417, 35796031; Phenotypes: erythrokeratodermia variabilis MONDO:0017851; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiac conduction disease v0.33 TRPM4 Bryony Thompson Marked gene: TRPM4 as ready
Cardiac conduction disease v0.33 TRPM4 Bryony Thompson Gene: trpm4 has been classified as Amber List (Moderate Evidence).
Cardiac conduction disease v0.33 TRPM4 Bryony Thompson Classified gene: TRPM4 as Amber List (moderate evidence)
Cardiac conduction disease v0.33 TRPM4 Bryony Thompson Gene: trpm4 has been classified as Amber List (Moderate Evidence).
Cardiac conduction disease v0.32 TRPM4 Bryony Thompson gene: TRPM4 was added
gene: TRPM4 was added to Cardiac conduction disease. Sources: NHS GMS
Mode of inheritance for gene: TRPM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPM4 were set to 19726882; 26820365; 21887725; 32681584; 20562447; 25531103; 27207958; 29568272; 29748318; 36352534; 35205305
Phenotypes for gene: TRPM4 were set to progressive familial heart block type IB MONDO:0011474
Mode of pathogenicity for gene: TRPM4 was set to Other
Review for gene: TRPM4 was set to AMBER
Added comment: A lot of the originally reported variants are more common in gnomAD than is expected for a dominant condition. However, there are at least 2 families that have decent segregation evidence and that suggest gain of function is the mechanism of disease. Loss of function variants are common in gnomAD.
Publications that contribute to gene-disease association:
PMID: 19726882 - linkage analysis in a large South African Afrikaner family with progressive familial heart block identified linkage to chromosomal locus 19q13.3. p.E7K was found to segregate with PFHB in the family. The variant was found to lead to a gain of function. The variant is rare in gnomAD v4 - 2 hets.
PMID: 26820365 - identified 13 “rare” TRPM4 variants in 95 unrelated patients with progressive cardiac conduction disease (PCCD). Some of the variants are a bit too common in gnomAD to be associated with dominant disease. One of the variants (p.Ile376Thr - 3 hets in gnomAD v4) segregated with PCCD in a large French 4-generation pedigree. TRPM4-p.I376T results in an increased current density in patch-clamp assays & augmented TRPM4 channel expression at the cell surface.
PMID: 21887725 - 8 “rare” TRPM4 variants identified in 160 cases with cardiac conduction disturbances. 3 of the variants had some supporting segregation evidence (Y790H - 3 segs, P970S - 1 seg, K914R - 1 seg)
PMID: 32681584 - in vitro functional assays on K914R which demonstrate a gain of function
Publications with uncertainty:
PMID: 20562447 - 3 families with dominant isolated cardiac conduction blocks were used for linkage analysis and a genomic interval on the long arm of chromosome 19 in an interval of ~300 genes. Screened 12 genes. TRPM4 p.Ala432Thr (L1 family), p.Arg164Trp (F1 family), p.Gly844Asp (F2 family). Ala432Thr and Gly844Asp are too common in gnomAD for a Mendelian AD disease (see below). Incomplete penetrance for p.Arg164Trp in family F1. All 3 variants increased current density in patch-clamp assays compared to WT (p<0.05).
PMID: 25531103 - null mouse model has cardiac hypertrophy and electrophysiological alterations
PMID: 27207958 - “rare” missense variants identified in children with atrioventricular block. Asp198Gly (2 hets in gnomAD v4), Ala432Thr/Gly582Ser present in 2 families (A432T - 558 alleles, 5 homs; G582S - 604 alleles, 7 homs in gnomAD v4) and also carried variants in SCN5 & NKX2.5, Thr677Ile (1 het in gnomAD v4), Val921Ile (101 alleles, 1 hom in gnomAD v4). Ala432Thr/Gly582Ser demonstrated loss of function in patch clamp assay - A432T alone was LoF, while G582S alone was GoF. D198G, T677I, and V921I didn’t alter function in the assays
PMID: 29568272 - p.A101T (3299 alleles, 51 homs), p.Q854R (1610 alleles, 5 homs), p.S1044C (7 hets), p.A101T/P1204L (5013 alleles, 11 homs). In patch-clamp assays, all variants reduced current except Q854R which increased the current (GoF)
PMID: 29748318 - synonymous variant c.858G>A shown to lead to exon 7 skipping, expected to cause loss of function identified in 2 siblings with cardiac conduction defects. It was inherited from apparently unaffected mother
PMID: 36352534, 35205305 - both report TRPM4 c.2351G>A, p.Gly844Asp in association with conduction disease. However, the variant is highly prevalent in gnomAD v4 (2200 alleles, 1 homozygote)
Sources: NHS GMS
Cardiac conduction disease v0.31 TBX5 Bryony Thompson Marked gene: TBX5 as ready
Cardiac conduction disease v0.31 TBX5 Bryony Thompson Gene: tbx5 has been classified as Green List (High Evidence).
Cardiac conduction disease v0.31 TBX5 Bryony Thompson Classified gene: TBX5 as Green List (high evidence)
Cardiac conduction disease v0.31 TBX5 Bryony Thompson Gene: tbx5 has been classified as Green List (High Evidence).
Cardiac conduction disease v0.30 TBX5 Bryony Thompson gene: TBX5 was added
gene: TBX5 was added to Cardiac conduction disease. Sources: NHS GMS
Mode of inheritance for gene: TBX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBX5 were set to 20301290
Phenotypes for gene: TBX5 were set to Holt-Oram syndrome MONDO:0007732
Review for gene: TBX5 was set to GREEN
gene: TBX5 was marked as current diagnostic
Added comment: Conduction disease is a characteristic feature of the condition.
Sources: NHS GMS
Cardiac conduction disease v0.29 SCN1B Bryony Thompson Marked gene: SCN1B as ready
Cardiac conduction disease v0.29 SCN1B Bryony Thompson Gene: scn1b has been classified as Amber List (Moderate Evidence).
Cardiac conduction disease v0.29 SCN1B Bryony Thompson Classified gene: SCN1B as Amber List (moderate evidence)
Cardiac conduction disease v0.29 SCN1B Bryony Thompson Gene: scn1b has been classified as Amber List (Moderate Evidence).
Cardiac conduction disease v0.28 SCN1B Bryony Thompson gene: SCN1B was added
gene: SCN1B was added to Cardiac conduction disease. Sources: NHS GMS
Mode of inheritance for gene: SCN1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN1B were set to 19808477; 18464934; 28878239; 29758173
Phenotypes for gene: SCN1B were set to Heart conduction disease MONDO:0000992
Review for gene: SCN1B was set to AMBER
Added comment: This gene is disputed for Brugada syndrome. There is a single family reported with decent segregation evidence of a missense variant (p.Glu87Gln) with conduction disease, and another missense that has been reported in a case with AF, that has been reported as pathogenic for epilepsy.
PMID: 19808477 - R85H (8 hets in gnomAD v4) identified in a case with atrial fibrillation. This variant has also been reported in patients with GEFS and is reported LP/P in ClinVar. D153N (277 hets in gnomAD v4) also identified in a case with AF, but the variant is classified as a VUS.
PMID: 18464934 - Glu87Gln (3 hets in gnomAD v4) identified in a Turkish family with 2 siblings with conduction abnormalities, inherited from mother with no cardiac phenotype (later determined to have clinical atrioventricular nodal reentry tachycardia in PMID: 29758173). c.536G>A Trp179Ter in beta1B transcript (NM_001037.5:c.448+88G>A - 44 hets gnomAD v4) identified in a family with conduction disease (3 affected cases & 1 unaffected individual). c.537G>A p.Trp179Ter (NM_001037.5(SCN1B):c.448+89G>A - 1 het in gnomAD v4) identified in fam 3 - 1 affected case & 1 unaffected individual. Haploinsufficiency is the suggested mechanism of disease supported by electrophysiologic data.
PMID: 28878239 - in vitro functional assays suggesting Glu87Gln reduces sodium channel function.
PMID: 29758173 - study suggesting p.Trp179Ter is not associated with disease, but has updated information for the Turkish family with p.Glu87Gln strengthening the segregation of the variant with conduction disease
Sources: NHS GMS
Mendeliome v1.2443 ATP11A Sangavi Sivagnanasundram changed review comment from: PMID: 39432785 (upgraded to GREEN on leukodystrophy panel)
3 unrelated probands with variable neurological features presenting in childhood however only two presented with leukodystrophy like symptoms
Patient 1 (canadian) and 3 (USA) showed bilateral hypomyelination on brain MRI

PMID: 40185629 - refractory focal epilepsy (AMBER for epilepsy)
chinese probands - childhood cases
De novo missense variants were identified in the two unrelated probands of chinese descent
Case 1 - female patient experiencing epileptic seizures from the age of 4 - Lys812Ile
Case 2 - male patient experienceing epileptic seizures from the age of 7 - Trp1036Cys; to: PMID: 39432785 (upgraded to GREEN on leukodystrophy panel)
3 unrelated probands with variable neurological features presenting in childhood however only two presented with leukodystrophy like symptoms
Patient 1 (canadian) and 3 (USA) showed bilateral hypomyelination on brain MRI

PMID: 40185629 - Two chinese individuals reported with refractory focal epilepsy (AMBER for epilepsy)

De novo missense variants were identified in the two unrelated probands of chinese descent
Case 1 - female patient experiencing epileptic seizures from the age of 4 - Lys812Ile
Case 2 - male patient experienceing epileptic seizures from the age of 7 - Trp1036Cys
Genetic Epilepsy v1.124 ATP11A Sangavi Sivagnanasundram gene: ATP11A was added
gene: ATP11A was added to Genetic Epilepsy. Sources: Other
Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP11A were set to 40185629
Phenotypes for gene: ATP11A were set to Focal Epilepsy MONDO:0005384
Review for gene: ATP11A was set to AMBER
Added comment: PMID: 40185629 - Two chinese individuals reported with refractory focal epilepsy

De novo missense variants were identified in the two unrelated probands of chinese descent
Case 1 - female patient experiencing epileptic seizures from the age of 4 - Lys812Ile
Case 2 - male patient experienceing epileptic seizures from the age of 7 - Trp1036Cys
Sources: Other
Mendeliome v1.2443 ATP11A Sangavi Sivagnanasundram reviewed gene: ATP11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39432785, 40185629; Phenotypes: leukodystrophy, hypomyelinating, 24, MONDO:0859242, Focal epilepsy MONDO:0005384; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Leukodystrophy - paediatric v0.318 ATP11A Sangavi Sivagnanasundram reviewed gene: ATP11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39432785; Phenotypes: leukodystrophy, hypomyelinating, 24, MONDO:0859242; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Lysosomal Storage Disorder v1.17 AP5B1 Bryony Thompson Marked gene: AP5B1 as ready
Lysosomal Storage Disorder v1.17 AP5B1 Bryony Thompson Gene: ap5b1 has been classified as Amber List (Moderate Evidence).
Lysosomal Storage Disorder v1.17 AP5B1 Bryony Thompson Classified gene: AP5B1 as Amber List (moderate evidence)
Lysosomal Storage Disorder v1.17 AP5B1 Bryony Thompson Gene: ap5b1 has been classified as Amber List (Moderate Evidence).
Lysosomal Storage Disorder v1.16 AP5B1 Bryony Thompson gene: AP5B1 was added
gene: AP5B1 was added to Lysosomal Storage Disorder. Sources: Literature
Mode of inheritance for gene: AP5B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5B1 were set to 40081374
Phenotypes for gene: AP5B1 were set to Hereditary macular dystrophy MONDO:0020242, AP-5 complex-related
Review for gene: AP5B1 was set to AMBER
Added comment: Currently only 2 unrelated cases with macular dystrophy (1 hom & 1 chet). The study also presents sufficient evidence for an association of another AP-5 complex gene (AP5Z1) with macular dystrophy. AP-5 complex proteins (AP5Z1, AP5M1, and AP5B1) display punctate localization in human RPE explants. The AP-5 complex containing AP5Z1, AP5M1, and AP5B1, is integral to lysosome function. AP-5 deficiency results in the accumulation of aberrant endolysosomes, which is a lysosome storage disorder.
Sources: Literature
Macular Dystrophy/Stargardt Disease v0.51 AP5B1 Bryony Thompson Marked gene: AP5B1 as ready
Macular Dystrophy/Stargardt Disease v0.51 AP5B1 Bryony Thompson Gene: ap5b1 has been classified as Amber List (Moderate Evidence).
Macular Dystrophy/Stargardt Disease v0.51 AP5B1 Bryony Thompson Classified gene: AP5B1 as Amber List (moderate evidence)
Macular Dystrophy/Stargardt Disease v0.51 AP5B1 Bryony Thompson Gene: ap5b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2443 AP5B1 Bryony Thompson Marked gene: AP5B1 as ready
Mendeliome v1.2443 AP5B1 Bryony Thompson Gene: ap5b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2443 AP5B1 Bryony Thompson Classified gene: AP5B1 as Amber List (moderate evidence)
Mendeliome v1.2443 AP5B1 Bryony Thompson Gene: ap5b1 has been classified as Amber List (Moderate Evidence).
Macular Dystrophy/Stargardt Disease v0.50 AP5B1 Bryony Thompson gene: AP5B1 was added
gene: AP5B1 was added to Macular Dystrophy/Stargardt Disease. Sources: Literature
Mode of inheritance for gene: AP5B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5B1 were set to 40081374
Phenotypes for gene: AP5B1 were set to Hereditary macular dystrophy MONDO:0020242, AP-5 complex-related
Review for gene: AP5B1 was set to AMBER
Added comment: Currently only 2 unrelated cases with macular dystrophy (1 hom & 1 chet). The study also presents sufficient evidence for an association of another AP-5 complex gene (AP5Z1) with macular dystrophy. AP-5 complex proteins (AP5Z1, AP5M1, and AP5B1) display punctate localization in human RPE explants.
Sources: Literature
Mendeliome v1.2442 AP5B1 Bryony Thompson gene: AP5B1 was added
gene: AP5B1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AP5B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5B1 were set to 40081374
Phenotypes for gene: AP5B1 were set to Hereditary macular dystrophy MONDO:0020242, AP-5 complex-related
Review for gene: AP5B1 was set to AMBER
Added comment: Currently only 2 unrelated cases with macular dystrophy (1 hom & 1 chet). The study also presents sufficient evidence for an association of another AP-5 complex gene (AP5Z1) with macular dystrophy. AP-5 complex proteins (AP5Z1, AP5M1, and AP5B1) display punctate localization in human RPE explants.
Sources: Literature
Mendeliome v1.2441 AP5M1 Bryony Thompson Marked gene: AP5M1 as ready
Mendeliome v1.2441 AP5M1 Bryony Thompson Gene: ap5m1 has been classified as Green List (High Evidence).
Lysosomal Storage Disorder v1.15 AP5M1 Bryony Thompson Classified gene: AP5M1 as Green List (high evidence)
Lysosomal Storage Disorder v1.15 AP5M1 Bryony Thompson Gene: ap5m1 has been classified as Green List (High Evidence).
Lysosomal Storage Disorder v1.14 AP5M1 Bryony Thompson gene: AP5M1 was added
gene: AP5M1 was added to Lysosomal Storage Disorder. Sources: Literature
Mode of inheritance for gene: AP5M1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5M1 were set to 40081374
Phenotypes for gene: AP5M1 were set to Hereditary macular dystrophy MONDO:0020242, AP-5 complex-related
Review for gene: AP5M1 was set to GREEN
Added comment: 3 unrelated cases with macular dystrophy and homozygous variants (2x nonsense & a missense). The study also presents sufficient evidence for an association of another AP-5 complex gene (AP5Z1) with macular dystrophy. AP-5 complex proteins (AP5Z1, AP5M1, and AP5B1) display punctate localization in human RPE explants. The AP-5 complex containing AP5Z1, AP5M1, and AP5B1, is integral to lysosome function. AP-5 deficiency results in the accumulation of aberrant endolysosomes, which is a lysosome storage disorder.
Sources: Literature
Lysosomal Storage Disorder v1.13 AP5Z1 Bryony Thompson Marked gene: AP5Z1 as ready
Lysosomal Storage Disorder v1.13 AP5Z1 Bryony Thompson Gene: ap5z1 has been classified as Green List (High Evidence).
Lysosomal Storage Disorder v1.13 AP5Z1 Bryony Thompson reviewed gene: AP5Z1: Rating: GREEN; Mode of pathogenicity: None; Publications: 40081374, 29381698, 26085577; Phenotypes: Spastic paraplegia 48, autosomal recessive, MIM# 613647; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Macular Dystrophy/Stargardt Disease v0.49 AP5M1 Bryony Thompson Marked gene: AP5M1 as ready
Macular Dystrophy/Stargardt Disease v0.49 AP5M1 Bryony Thompson Gene: ap5m1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.49 AP5M1 Bryony Thompson Classified gene: AP5M1 as Green List (high evidence)
Macular Dystrophy/Stargardt Disease v0.49 AP5M1 Bryony Thompson Gene: ap5m1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.48 AP5M1 Bryony Thompson gene: AP5M1 was added
gene: AP5M1 was added to Macular Dystrophy/Stargardt Disease. Sources: Literature
Mode of inheritance for gene: AP5M1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5M1 were set to 40081374
Phenotypes for gene: AP5M1 were set to Hereditary macular dystrophy MONDO:0020242, AP-5 complex-related
Review for gene: AP5M1 was set to GREEN
Added comment: 3 unrelated cases with macular dystrophy and homozygous variants (2x nonsense & a missense). The study also presents sufficient evidence for an association of another AP-5 complex gene (AP5Z1) with macular dystrophy. AP-5 complex proteins (AP5Z1, AP5M1, and AP5B1) display punctate localization in human RPE explants.
Sources: Literature
Mendeliome v1.2441 AP5M1 Bryony Thompson Classified gene: AP5M1 as Green List (high evidence)
Mendeliome v1.2441 AP5M1 Bryony Thompson Gene: ap5m1 has been classified as Green List (High Evidence).
Mendeliome v1.2440 AP5M1 Bryony Thompson gene: AP5M1 was added
gene: AP5M1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AP5M1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5M1 were set to 40081374
Phenotypes for gene: AP5M1 were set to Hereditary macular dystrophy MONDO:0020242, AP-5 complex-related
Review for gene: AP5M1 was set to GREEN
Added comment: 3 unrelated cases with macular dystrophy and homozygous variants (2x nonsense & a missense). The study also presents sufficient evidence for an association of another AP-5 complex gene (AP5Z1) with macular dystrophy. AP-5 complex proteins (AP5Z1, AP5M1, and AP5B1) display punctate localization in human RPE explants.
Sources: Literature
Mendeliome v1.2439 AP5Z1 Bryony Thompson reviewed gene: AP5Z1: Rating: GREEN; Mode of pathogenicity: None; Publications: 40081374, 33543803; Phenotypes: Spastic paraplegia 48, autosomal recessive, MIM# 613647, MONDO:0013342, Hereditary macular dystrophy MONDO:0020242; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Macular Dystrophy/Stargardt Disease v0.47 AP5Z1 Bryony Thompson Marked gene: AP5Z1 as ready
Macular Dystrophy/Stargardt Disease v0.47 AP5Z1 Bryony Thompson Gene: ap5z1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.47 AP5Z1 Bryony Thompson Classified gene: AP5Z1 as Green List (high evidence)
Macular Dystrophy/Stargardt Disease v0.47 AP5Z1 Bryony Thompson Gene: ap5z1 has been classified as Green List (High Evidence).
Macular Dystrophy/Stargardt Disease v0.46 AP5Z1 Bryony Thompson gene: AP5Z1 was added
gene: AP5Z1 was added to Macular Dystrophy/Stargardt Disease. Sources: Literature
Mode of inheritance for gene: AP5Z1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP5Z1 were set to 40081374
Phenotypes for gene: AP5Z1 were set to Hereditary macular dystrophy MONDO:0020242
Review for gene: AP5Z1 was set to GREEN
gene: AP5Z1 was marked as current diagnostic
Added comment: 14 families reported with biallelic variants in AP5Z1 with mainly adult-onset macular dystrophy, isolated or with extraocular features (including Parkinsonism, mild ID, HSP, peripheral neuropathy, hearing loss). The authors' suggest that macular dystrophy could be a presenting feature before HSP (or other extraocular features).
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v1.90 AP5Z1 Bryony Thompson Classified gene: AP5Z1 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.90 AP5Z1 Bryony Thompson Gene: ap5z1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.89 AP5Z1 Bryony Thompson reviewed gene: AP5Z1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39059408, 26085577, 33543803; Phenotypes: Spastic paraplegia 48, autosomal recessive, MIM# 613647; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital Heart Defect v0.439 KCTD10 Bryony Thompson Classified gene: KCTD10 as Green List (high evidence)
Congenital Heart Defect v0.439 KCTD10 Bryony Thompson Gene: kctd10 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.438 KCTD10 Bryony Thompson Classified gene: KCTD10 as Green List (high evidence)
Congenital Heart Defect v0.438 KCTD10 Bryony Thompson Gene: kctd10 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.437 KCTD10 Bryony Thompson Marked gene: KCTD10 as ready
Congenital Heart Defect v0.437 KCTD10 Bryony Thompson Gene: kctd10 has been classified as Red List (Low Evidence).
Mendeliome v1.2439 KCTD10 Bryony Thompson Marked gene: KCTD10 as ready
Mendeliome v1.2439 KCTD10 Bryony Thompson Gene: kctd10 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.437 KCTD10 Bryony Thompson gene: KCTD10 was added
gene: KCTD10 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: KCTD10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCTD10 were set to 24705121; 24430697; 38489388; 40121532
Phenotypes for gene: KCTD10 were set to multiple congenital anomalies/dysmorphic syndrome MONDO:0019042, KCTD10-related
Review for gene: KCTD10 was set to GREEN
Added comment: Two unrelated probands with multiple congenital anomalies, both with abnormalities of the cardiovascular system and confirmed de novo novel missense variants (p.R248Q and p.N169S). There were also additional individuals (<5) in the GeneDx in-house database who didn’t consent to case-level publication with confirmed de novo missesne variants in KCTD10 and overlapping phenotypes (100% with abnormalities of the cardiovascular system). Other congenital anomalies of different organs systems were present in 33-67% of the individuals. Further elucidation of the phenotypes associated with this gene are required. Additionally, null mouse and zebrafish models suggest Kctd10 is critical for cardiovascular development and is involved in the regulation of brain development.
Sources: Literature
Mendeliome v1.2439 KCTD10 Bryony Thompson Classified gene: KCTD10 as Green List (high evidence)
Mendeliome v1.2439 KCTD10 Bryony Thompson Gene: kctd10 has been classified as Green List (High Evidence).
Mendeliome v1.2438 KCTD10 Bryony Thompson gene: KCTD10 was added
gene: KCTD10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCTD10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCTD10 were set to 24705121; 24430697; 38489388; 40121532
Phenotypes for gene: KCTD10 were set to multiple congenital anomalies/dysmorphic syndrome MONDO:0019042, KCTD10-related
Review for gene: KCTD10 was set to GREEN
Added comment: Two unrelated probands with multiple congenital anomalies, both with abnormalities of the cardiovascular system and confirmed de novo novel missense variants (p.R248Q and p.N169S). There were also additional individuals (<5) in the GeneDx in-house database who didn’t consent to case-level publication with confirmed de novo missesne variants in KCTD10 and overlapping phenotypes (100% with abnormalities of the cardiovascular system). Other congenital anomalies of different organs systems were present in 33-67% of the individuals. Further elucidation of the phenotypes associated with this gene are required. Additionally, null mouse and zebrafish models suggest Kctd10 is critical for cardiovascular development and is involved in the regulation of brain development.
Sources: Literature
Mendeliome v1.2437 ATP6V1B1 Sarah Leigh reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39837581, 9916796, 12566520, 18798332; Phenotypes: Distal renal tubular acidosis 2 with progressive sensorineural hearing loss, MIM#267300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 COL11A2 Melanie Marty edited their review of gene: COL11A2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1868 COL11A2 Melanie Marty changed review comment from: The gene-disease association with otospondylomegaepiphyseal dysplasia is well established (DEFINITIVE) by ClinGen, and deafness is part of the phenotype, both mono-allelic and bi-allelic variants are reported. Otospondylomegaepiphyseal dysplasia AD (OSMED, MIM#184840) is also known as non-ocular Stickler syndrome or Type III Stickler syndrome.

There are also a number of reports of mono-allelic and bi-allelic variants associated with isolated deafness (PMIDs: 10581026;25633957;16033917), and rated as MODERATE by ClinGen for AR and DEFINITIVE for AD. Bi-allelic variants are associated with severe pre lingual deafness.

Fibrochondrogenesis 2 a severe skeletal dysplasia is associated with AD and AR.; to: The gene-disease association with otospondylomegaepiphyseal dysplasia is well established (DEFINITIVE) by ClinGen, and deafness is part of the phenotype, both mono-allelic and bi-allelic variants are reported. Otospondylomegaepiphyseal dysplasia AD (OSMED, MIM#184840) is also known as non-ocular Stickler syndrome or Type III Stickler syndrome.

There are also a number of reports of mono-allelic and bi-allelic variants associated with isolated deafness (PMIDs: 10581026;25633957;16033917), and rated as MODERATE by ClinGen for AR and DEFINITIVE for AD. Bi-allelic variants are associated with severe pre lingual deafness.

Fibrochondrogenesis 2 a severe skeletal dysplasia is associated with AD and AR.

Only including the AR phenotypes for this screening panel.
Prepair 1000+ v1.1868 COL11A2 Melanie Marty reviewed gene: COL11A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10581026, 25633957, 16033917, 25240749, 22796475, 20112039; Phenotypes: Deafness, autosomal recessive 53 MIM#609706, Fibrochondrogenesis 2 MIM#614524, Otospondylomegaepiphyseal dysplasia, autosomal recessive MIM#215150; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2437 CDKL2 Zornitza Stark Marked gene: CDKL2 as ready
Mendeliome v1.2437 CDKL2 Zornitza Stark Gene: cdkl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2437 CDKL2 Zornitza Stark Classified gene: CDKL2 as Amber List (moderate evidence)
Mendeliome v1.2437 CDKL2 Zornitza Stark Gene: cdkl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2436 CDKL2 Zornitza Stark reviewed gene: CDKL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CDKL2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.98 CDKL2 Zornitza Stark Marked gene: CDKL2 as ready
Intellectual disability syndromic and non-syndromic v1.98 CDKL2 Zornitza Stark Gene: cdkl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.98 CDKL2 Zornitza Stark Classified gene: CDKL2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.98 CDKL2 Zornitza Stark Gene: cdkl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.97 CDKL2 Zornitza Stark reviewed gene: CDKL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CDKL2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v0.29 STAG3 Jasmine Chew gene: STAG3 was added
gene: STAG3 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: STAG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAG3 were set to 24597867; 26059840; 28393351; 30006057; 32634216; 31125047; 31682730
Phenotypes for gene: STAG3 were set to Premature ovarian failure 8, MIM# 615723; Spermatogenic failure 61, MIM# 619672
Added comment: Literature in OMIM (PMID:24597867; 26059840; 28393351;30006057;32634216; 31125047; 31682730)- biallelic missense and LOF variants reported in conjunction with primary ovarian failure and spermatogenic failure

New papers reporting biallelic LOF variants for POI- PMID: 34497033; 35503298

New papers reporting biallelic LOF variants for NOA- PMID: 33980954

New papers reporting biallelic LOF variants for both POI and NOA in familial cases- PMID: 39932630; 35176428
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.29 ZP2 Jasmine Chew edited their review of gene: ZP2: Changed rating: GREEN
Infertility and Recurrent Pregnancy Loss v0.29 MSH4 Jasmine Chew gene: MSH4 was added
gene: MSH4 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: MSH4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MSH4 were set to 28541421; 33448284; 34755185; 33437391; 33448284; 35090489; 34755185; 38175272; 37620942
Phenotypes for gene: MSH4 were set to Premature ovarian failure 20, MIM# 619938; Spermatogenic failure 2, MIM# 108420
Review for gene: MSH4 was set to GREEN
Added comment: Literature in OMIM (PMID:28541421;33448284; 34755185;33437391;33448284; 35090489; 34755185)- biallelic LOF and missense variants reported in multiple familial cases with premature ovarian failure and spermatogenic failure/azoospermia

New papers:
i) PMID: 38175272- novel homozygous nonsense variant ( p.Q40*) in an Iranian family with four affected members consisting of two NOA men with maturation arrest and two women with POI. This variant occurs at the beginning of MSH4 and leads to the formation of a very short chain with 39 residues or complete loss of protein, which it is likely the main reason for the emergence of POI and NOA. Testicular sperm retrieval and ovarian stimulation cycles have not been successful in any of patients.

ii) PMID: 37620942- compound heterozygous variants (p.Thr792Ala and p.Lys741Argfs*2) in a woman with diminished ovarian reserve (DOR), presented with poor oocyte quantity and quality, resulting in unsuccessful in vitro fertilization cycles. Bioinformatics and in vitro functional analysis showed that the p.Thr792Ala variant altered the local conformation of the MutS_V domain without decreasing MSH4 protein expression, while the p.Lys741Argfs*2 variant led to a reduction in MSH4 protein expression without impacting splicing.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.97 CDKL1 Zornitza Stark Marked gene: CDKL1 as ready
Intellectual disability syndromic and non-syndromic v1.97 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.97 CDKL1 Zornitza Stark Classified gene: CDKL1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v1.97 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v1.96 CDKL1 Zornitza Stark reviewed gene: CDKL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CDKL1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2436 CDKL1 Zornitza Stark Marked gene: CDKL1 as ready
Mendeliome v1.2436 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Red List (Low Evidence).
Mendeliome v1.2436 CDKL1 Zornitza Stark Classified gene: CDKL1 as Red List (low evidence)
Mendeliome v1.2436 CDKL1 Zornitza Stark Gene: cdkl1 has been classified as Red List (Low Evidence).
Mendeliome v1.2435 CDKL1 Zornitza Stark reviewed gene: CDKL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CDKL1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.1868 TRIT1 Zornitza Stark Marked gene: TRIT1 as ready
Prepair 1000+ v1.1868 TRIT1 Zornitza Stark Gene: trit1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1868 TRIT1 Zornitza Stark Phenotypes for gene: TRIT1 were changed from Combined oxidative phosphorylation deficiency 35, 617873 (3), Autosomal recessive to Combined oxidative phosphorylation deficiency 35 MIM#617873
Prepair 1000+ v1.1867 TRIT1 Zornitza Stark Publications for gene: TRIT1 were set to
Prepair 1000+ v1.1866 NEB Zornitza Stark Publications for gene: NEB were set to 27228465
Prepair 500+ v1.7 OSGEP Zornitza Stark Marked gene: OSGEP as ready
Prepair 500+ v1.7 OSGEP Zornitza Stark Gene: osgep has been classified as Green List (High Evidence).
Prepair 500+ v1.7 OSGEP Zornitza Stark Phenotypes for gene: OSGEP were changed from Galloway-Mowat syndrome 3, 617729 (3), Autosomal recessive to Galloway-Mowat syndrome 3, MIM# 617729
Prepair 500+ v1.6 OSGEP Zornitza Stark Publications for gene: OSGEP were set to
Prepair 1000+ v1.1865 OSTM1 Zornitza Stark Marked gene: OSTM1 as ready
Prepair 1000+ v1.1865 OSTM1 Zornitza Stark Gene: ostm1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1865 OSTM1 Zornitza Stark Phenotypes for gene: OSTM1 were changed from Osteopetrosis, autosomal recessive 5, 259720 (3) to Osteopetrosis, autosomal recessive 5, MIM#259720
Prepair 1000+ v1.1864 OSTM1 Zornitza Stark Publications for gene: OSTM1 were set to
Prepair 1000+ v1.1863 OSTM1 Zornitza Stark reviewed gene: OSTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 5, MIM#259720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1863 PCDH15 Zornitza Stark Marked gene: PCDH15 as ready
Prepair 1000+ v1.1863 PCDH15 Zornitza Stark Gene: pcdh15 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1863 PCDH15 Zornitza Stark Phenotypes for gene: PCDH15 were changed from Usher syndrome, type 1F, 602083 (3) to Usher syndrome, type 1F, MIM# 602083
Prepair 1000+ v1.1862 PCDH15 Zornitza Stark Publications for gene: PCDH15 were set to
Prepair 1000+ v1.1861 SLC39A8 Zornitza Stark Marked gene: SLC39A8 as ready
Prepair 1000+ v1.1861 SLC39A8 Zornitza Stark Gene: slc39a8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1861 SLC39A8 Zornitza Stark Phenotypes for gene: SLC39A8 were changed from Congenital disorder of glycosylation, type IIn, 616721 (3), Autosomal recessive to Congenital disorder of glycosylation, type IIn MIM#616721
Prepair 1000+ v1.1860 SLC39A8 Zornitza Stark Publications for gene: SLC39A8 were set to
Prepair 1000+ v1.1859 SRD5A3 Zornitza Stark Marked gene: SRD5A3 as ready
Prepair 1000+ v1.1859 SRD5A3 Zornitza Stark Gene: srd5a3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1859 SRD5A3 Zornitza Stark Phenotypes for gene: SRD5A3 were changed from Congenital disorder of glycosylation, type Iq, 612379 (3) to Congenital disorder of glycosylation, type Iq MIM#612379; Kahrizi syndrome#612713; SRD5A3-congenital disorder of glycosylation (MONDO:0012885)
Prepair 1000+ v1.1858 SRD5A3 Zornitza Stark Publications for gene: SRD5A3 were set to
Prepair 1000+ v1.1857 TBC1D23 Zornitza Stark Marked gene: TBC1D23 as ready
Prepair 1000+ v1.1857 TBC1D23 Zornitza Stark Gene: tbc1d23 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1857 TBC1D23 Zornitza Stark Phenotypes for gene: TBC1D23 were changed from Pontocerebellar hypoplasia, type 11, 617695 (3), Autosomal recessive to Pontocerebellar hypoplasia, type 11, MIM#617695
Prepair 1000+ v1.1856 TBC1D23 Zornitza Stark Publications for gene: TBC1D23 were set to
Prepair 1000+ v1.1855 LRSAM1 Zornitza Stark Tag for review tag was added to gene: LRSAM1.
Prepair 1000+ v1.1855 TCIRG1 Zornitza Stark Marked gene: TCIRG1 as ready
Prepair 1000+ v1.1855 TCIRG1 Zornitza Stark Gene: tcirg1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1855 TCIRG1 Zornitza Stark Phenotypes for gene: TCIRG1 were changed from Osteopetrosis, autosomal recessive 1, 259700 (3) to Osteopetrosis, autosomal recessive 1 MIM#259700
Prepair 1000+ v1.1854 TCIRG1 Zornitza Stark Publications for gene: TCIRG1 were set to
Prepair 1000+ v1.1853 PEX7 Zornitza Stark Marked gene: PEX7 as ready
Prepair 1000+ v1.1853 PEX7 Zornitza Stark Gene: pex7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1853 PEX7 Zornitza Stark Phenotypes for gene: PEX7 were changed from Chondrodysplasia punctata, rhizomelic, type 1, 215100 (3) to Peroxisome biogenesis disorder 9B, MIM# 614879; Rhizomelic chondrodysplasia punctata, type 1, MIM# 215100
Prepair 1000+ v1.1852 PEX7 Zornitza Stark Publications for gene: PEX7 were set to
Prepair 1000+ v1.1851 PGAP1 Zornitza Stark Marked gene: PGAP1 as ready
Prepair 1000+ v1.1851 PGAP1 Zornitza Stark Gene: pgap1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1851 PGAP1 Zornitza Stark Phenotypes for gene: PGAP1 were changed from Mental retardation, autosomal recessive 42, 615802 (3), Autosomal recessive to Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities, MIM# 615802
Prepair 1000+ v1.1850 PGAP1 Zornitza Stark Publications for gene: PGAP1 were set to
Prepair 1000+ v1.1849 POC1A Zornitza Stark Marked gene: POC1A as ready
Prepair 1000+ v1.1849 POC1A Zornitza Stark Gene: poc1a has been classified as Green List (High Evidence).
Prepair 1000+ v1.1849 POC1A Zornitza Stark Phenotypes for gene: POC1A were changed from Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, 614813 (3) to Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM# 614813
Prepair 1000+ v1.1848 POC1A Zornitza Stark Publications for gene: POC1A were set to
Infertility and Recurrent Pregnancy Loss v0.29 FSHB Jasmine Chew edited their review of gene: FSHB: Changed rating: GREEN
Infertility and Recurrent Pregnancy Loss v0.29 FSHB Jasmine Chew gene: FSHB was added
gene: FSHB was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: FSHB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FSHB were set to 8220432; 8220432; 9624193; 9806482; 12161499
Phenotypes for gene: FSHB were set to Hypogonadotropic hypogonadism 24 without anosmia, MIM# 229070
Added comment: Literature in OMIM (PMID:8220432;8220432;9624193;9806482;12161499)- multiple unrelated infertile women and males with isolated FSH deficiency carrying biallelic LOF variants
Sources: Literature
Prepair 1000+ v1.1847 PPA2 Zornitza Stark Marked gene: PPA2 as ready
Prepair 1000+ v1.1847 PPA2 Zornitza Stark Gene: ppa2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1847 PPA2 Zornitza Stark Phenotypes for gene: PPA2 were changed from Sudden cardiac failure, infantile, 617222 (3), Autosomal recessive to Sudden cardiac failure, infantile, MIM#617222; Sudden cardiac failure, alcohol-induced, MIM#617223
Prepair 1000+ v1.1846 PPA2 Zornitza Stark Publications for gene: PPA2 were set to
Prepair 1000+ v1.1845 VPS33B Zornitza Stark Marked gene: VPS33B as ready
Prepair 1000+ v1.1845 VPS33B Zornitza Stark Gene: vps33b has been classified as Green List (High Evidence).
Prepair 1000+ v1.1845 VPS33B Zornitza Stark Phenotypes for gene: VPS33B were changed from Arthrogryposis, renal dysfunction, and cholestasis 1, 208085 (3) to Arthrogryposis, renal dysfunction, and cholestasis 1 MIM#208085; Cholestasis, progressive familial intrahepatic, 12 MIM#620010; Keratoderma-ichthyosis-deafness syndrome, autosomal recessive MIM#620009
Prepair 1000+ v1.1844 VPS33B Zornitza Stark Publications for gene: VPS33B were set to
Prepair 1000+ v1.1843 PRDM12 Zornitza Stark Marked gene: PRDM12 as ready
Prepair 1000+ v1.1843 PRDM12 Zornitza Stark Gene: prdm12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1843 PRDM12 Zornitza Stark Phenotypes for gene: PRDM12 were changed from Neuropathy, hereditary sensory and autonomic, type VIII, 616488 (3), Autosomal recessive to Neuropathy, hereditary sensory and autonomic, type VIII, MIM# 616488
Prepair 1000+ v1.1842 PRDM12 Zornitza Stark Publications for gene: PRDM12 were set to
Prepair 1000+ v1.1841 PRX Zornitza Stark Marked gene: PRX as ready
Prepair 1000+ v1.1841 PRX Zornitza Stark Gene: prx has been classified as Green List (High Evidence).
Prepair 1000+ v1.1841 PRX Zornitza Stark Phenotypes for gene: PRX were changed from Dejerine-Sottas disease, 145900 (3) to Charcot-Marie-Tooth disease, type 4F, MIM# 614895; Dejerine-Sottas disease, MIM# 145900
Prepair 1000+ v1.1840 PRX Zornitza Stark Publications for gene: PRX were set to
Prepair 1000+ v1.1839 PUS1 Zornitza Stark Marked gene: PUS1 as ready
Prepair 1000+ v1.1839 PUS1 Zornitza Stark Gene: pus1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1839 PUS1 Zornitza Stark Phenotypes for gene: PUS1 were changed from Mitochondrial myopathy and sideroblastic anemia 1, 600462 (3) to Myopathy, lactic acidosis, and sideroblastic anemia 1, MIM# 600462
Prepair 1000+ v1.1838 PUS1 Zornitza Stark Publications for gene: PUS1 were set to
Prepair 1000+ v1.1837 QDPR Zornitza Stark Marked gene: QDPR as ready
Prepair 1000+ v1.1837 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Prepair 1000+ v1.1837 QDPR Zornitza Stark Phenotypes for gene: QDPR were changed from Hyperphenylalaninemia, BH4-deficient, C, 261630 (3) to Hyperphenylalaninemia, BH4-deficient, C, MIM# 261630
Prepair 1000+ v1.1836 QDPR Zornitza Stark Publications for gene: QDPR were set to
Prepair 1000+ v1.1835 RAB27A Zornitza Stark Marked gene: RAB27A as ready
Prepair 1000+ v1.1835 RAB27A Zornitza Stark Gene: rab27a has been classified as Green List (High Evidence).
Prepair 1000+ v1.1835 RAB27A Zornitza Stark Phenotypes for gene: RAB27A were changed from Griscelli syndrome, type 2, 607624 (3) to Griscelli syndrome, type 2, MIM# 607624
Prepair 1000+ v1.1834 RAB27A Zornitza Stark Publications for gene: RAB27A were set to
Prepair 1000+ v1.1833 RAD50 Zornitza Stark Marked gene: RAD50 as ready
Prepair 1000+ v1.1833 RAD50 Zornitza Stark Gene: rad50 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1833 RAD50 Zornitza Stark Phenotypes for gene: RAD50 were changed from Nijmegen breakage syndrome-like disorder, 613078 (3) to Nijmegen breakage syndrome-like disorder, MIM# 613078
Prepair 1000+ v1.1832 RAD50 Zornitza Stark Publications for gene: RAD50 were set to
Prepair 1000+ v1.1831 RPGRIP1L Zornitza Stark Marked gene: RPGRIP1L as ready
Prepair 1000+ v1.1831 RPGRIP1L Zornitza Stark Gene: rpgrip1l has been classified as Green List (High Evidence).
Prepair 1000+ v1.1831 RPGRIP1L Zornitza Stark Phenotypes for gene: RPGRIP1L were changed from Meckel syndrome 5, 611561 (3) to Joubert syndrome 7, MIM# 611560; Meckel syndrome 5, MIM# 611561; COACH syndrome 3, MIM# 619113; Ciliopathy, RPGRIP1L-related, MONDO:0005308
Prepair 1000+ v1.1830 RPGRIP1L Zornitza Stark Publications for gene: RPGRIP1L were set to
Infertility and Recurrent Pregnancy Loss v0.29 FSHR Jasmine Chew gene: FSHR was added
gene: FSHR was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: FSHR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FSHR were set to 7553856; 9769327; 11889179; 20087398; 12930927; 12930928; 17721928; 36704038
Phenotypes for gene: FSHR were set to Ovarian dysgenesis 1, MIM# 233300; Ovarian hyperstimulation syndrome, MIM# 608115
Added comment: Literature in OMIM-
i) biallelic variants for ovarian dysgenesis, supported by functional evidence- PMID:7553856; 9769327;11889179;20087398
ii) monoallelic variants for ovarian hyperstimulation syndrome- PMID:12930927;12930928;17721928

New paper:
i) PMID: 36704038- Novel compound heterozygous variants (Ala462Pro and p.Ala621Val) in a woman with primary ovarian insufficiency with resistant ovary syndrome. In vitro experiments revealed that the p.Ala462Pro variant resulted in barely detectable levels of intracellular signaling both in cAMP-dependent CRE-reporter activity and ERK activation and displayed a severely reduced plasma membrane receptor expression. In contrast, the p.Ala621Val variant resulted in partial loss of receptor activation without disruption of cell surface expression.
Sources: Literature
Prepair 1000+ v1.1829 SLC1A4 Zornitza Stark Marked gene: SLC1A4 as ready
Prepair 1000+ v1.1829 SLC1A4 Zornitza Stark Gene: slc1a4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1829 SLC1A4 Zornitza Stark Publications for gene: SLC1A4 were set to
Prepair 1000+ v1.1828 ABCB11 Zornitza Stark Marked gene: ABCB11 as ready
Prepair 1000+ v1.1828 ABCB11 Zornitza Stark Gene: abcb11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1828 ABCB11 Zornitza Stark Phenotypes for gene: ABCB11 were changed from Cholestasis, progressive familial intrahepatic 2, 601847 (3) to Cholestasis, progressive familial intrahepatic 2, MIM# 601847
Prepair 1000+ v1.1827 ABCB11 Zornitza Stark Publications for gene: ABCB11 were set to
Prepair 1000+ v1.1826 FITM2 Zornitza Stark Tag for review tag was added to gene: FITM2.
Infertility and Recurrent Pregnancy Loss v0.29 NLRP5 Zornitza Stark Marked gene: NLRP5 as ready
Infertility and Recurrent Pregnancy Loss v0.29 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.29 NLRP5 Zornitza Stark Classified gene: NLRP5 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.29 NLRP5 Zornitza Stark Gene: nlrp5 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.28 HFM1 Zornitza Stark Marked gene: HFM1 as ready
Infertility and Recurrent Pregnancy Loss v0.28 HFM1 Zornitza Stark Gene: hfm1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.28 HFM1 Zornitza Stark Classified gene: HFM1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.28 HFM1 Zornitza Stark Gene: hfm1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.27 GDF9 Zornitza Stark Marked gene: GDF9 as ready
Infertility and Recurrent Pregnancy Loss v0.27 GDF9 Zornitza Stark Gene: gdf9 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.27 GDF9 Zornitza Stark Classified gene: GDF9 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.27 GDF9 Zornitza Stark Gene: gdf9 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.26 KHDC3L Zornitza Stark Marked gene: KHDC3L as ready
Infertility and Recurrent Pregnancy Loss v0.26 KHDC3L Zornitza Stark Gene: khdc3l has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.26 KHDC3L Zornitza Stark Classified gene: KHDC3L as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.26 KHDC3L Zornitza Stark Gene: khdc3l has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.25 GDF9 Jasmine Chew gene: GDF9 was added
gene: GDF9 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: GDF9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GDF9 were set to 29044499; 33036707; 38643161
Phenotypes for gene: GDF9 were set to Premature ovarian failure 14, MIM# 618014
Review for gene: GDF9 was set to GREEN
Added comment: Literature in OMIM- PMID:29044499;33036707 - biallelic variants reported in women with premature ovarian failure, supported by functional evidence

New paper:
i) PMID: 38643161 (2024)- compound heterozygous variants (Q321X/S428T) in two infertile women with defect in follicle enlargement In vitro experiments confirmed that these variants caused reduction of GDF9 secretion, and/or alleviation in BMP15 binding. Moreover, Q308X/S415T mouse model was constructed, which recapitulated the phenotypes in probands with abnormal estrogen secretion and defected follicle enlargement. n addition, RNA sequencing of granulosa cells revealed the transcriptomic profiles related to defective follicle enlargement in theQ308X/S415T group.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.25 HFM1 Jasmine Chew changed review comment from: Literature in OMIM- PMID:24597873- compound heterozygous variants in a familial case and an unrelated individual with primary ovarian failure

New papers (single family with monoallelic variant and expansion of phenotypes in females)
i) PMID: 31279343- Novel heterozygous missense variant in HFM1 (c.3470G > A) in the proband and her mother both affected by POI. Minigene splicing assay of the WT and MT constructs revealed that an alternative splicing process were produced with the c.3470G > A variant in mRNA level.

ii) PMID: 35881270- novel compound heterozygous variants,c.1978-2A > C and c.2680 + 3_2680 + 4delAT, in two sisters with diminished ovarian reserve and recurrent pregnancy loss (RPL) in natural pregnancy and in vitro fertilization-embryo transfer (IVF-ET). Minigene assay showed that both variants could produce alternative transcripts compared to wild-type counterparts, which might result in protein dysfunction. These results demonstrated that RPL caused by the HFM1 gene might be inherited in AR mode,

iii) PMID: 36864181- novel homozygous splicing variant in HFM1 (NM_001017975.6: c.1730-1G > T) in two siblings - female with poor ovarian response and recurrent implantation failure and male with NOA. Minigene assay demonstrated that splicing variants caused abnormal alternative splicing of HFM1. For the sister, she experienced embryo arrest 9 weeks after pregnancy after undergoing 5 cycles of ART.

iv) PMID: 39929154- reported compound heterozygous variants c.1978-2A>C and c.2681-3T>A in a case of POI with unique genital characteristics; also their lit review showed that previous studies have linked HFM1 gene variants to clinical manifestations such as POI, diminished ovarian reserve, recurrent pregnancy loss, and poor outcomes in in vitro fertilization-embryo transfer.
Sources: Literature; to: Literature in OMIM- PMID:24597873- compound heterozygous variants in a familial case and an unrelated individual with primary ovarian failure

New papers (single family with monoallelic variant and expansion of phenotypes in females)
i) PMID: 31279343- Novel heterozygous missense variant in HFM1 (c.3470G > A) in the proband and her mother both affected by POI. Minigene splicing assay of the WT and MT constructs revealed that an alternative splicing process were produced with the c.3470G > A variant in mRNA level.

ii) PMID: 35881270- novel compound heterozygous variants,c.1978-2A > C and c.2680 + 3_2680 + 4delAT, in two sisters with diminished ovarian reserve and recurrent pregnancy loss (RPL) in natural pregnancy and in vitro fertilization-embryo transfer (IVF-ET). Minigene assay showed that both variants could produce alternative transcripts compared to wild-type counterparts, which might result in protein dysfunction. These results demonstrated that RPL caused by the HFM1 gene might be inherited in AR mode,

iii) PMID: 36864181- novel homozygous splicing variant in HFM1 (NM_001017975.6: c.1730-1G > T) in two siblings - female with poor ovarian response and recurrent implantation failure and male with NOA. Minigene assay demonstrated that splicing variants caused abnormal alternative splicing of HFM1. For the sister, she experienced embryo arrest 9 weeks after pregnancy after undergoing 5 cycles of ART.

iv) PMID: 39929154- reported compound heterozygous variants c.1978-2A>C and c.2681-3T>A in a case of POI with unique genital characteristics; also their lit review showed that previous studies have linked HFM1 gene variants to clinical manifestations such as POI, diminished ovarian reserve, recurrent pregnancy loss, and poor outcomes in in vitro fertilization-embryo transfer.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.25 HFM1 Jasmine Chew changed review comment from: Literature in OMIM- PMID:24597873- compound heterozygous variants in a familial case and an unrelated individual with primary ovarian failure

New papers (single family with monoallelic variant and expansion of phenotypes)
i) PMID: 31279343- Novel heterozygous missense variant in HFM1 (c.3470G > A) in the proband and her mother both affected by POI. Minigene splicing assay of the WT and MT constructs revealed that an alternative splicing process were produced with the c.3470G > A variant in mRNA level.

ii) PMID: 35881270- novel compound heterozygous variants,c.1978-2A > C and c.2680 + 3_2680 + 4delAT, in two sisters with diminished ovarian reserve and recurrent pregnancy loss (RPL) in natural pregnancy and in vitro fertilization-embryo transfer (IVF-ET). Minigene assay showed that both variants could produce alternative transcripts compared to wild-type counterparts, which might result in protein dysfunction. These results demonstrated that RPL caused by the HFM1 gene might be inherited in AR mode,

iii) PMID: 36864181 (2023)- novel homozygous splicing variant in HFM1 (NM_001017975.6: c.1730-1G > T) in two siblings - female with poor ovarian response and recurrent implantation failure and male with NOA. Minigene assay demonstrated that splicing variants caused abnormal alternative splicing of HFM1. For the sister, she experienced embryo arrest 9 weeks after pregnancy after undergoing 5 cycles of ART.

iv) PMID: 39929154 (2025)- reported compound heterozygous variants c.1978-2A>C and c.2681-3T>A in a case of POI with unique genital characteristics; also their lit review showed that previous studies have linked HFM1 gene variants to clinical manifestations such as POI, diminished ovarian reserve, recurrent pregnancy loss, and poor outcomes in in vitro fertilization-embryo transfer.
Sources: Literature; to: Literature in OMIM- PMID:24597873- compound heterozygous variants in a familial case and an unrelated individual with primary ovarian failure

New papers (single family with monoallelic variant and expansion of phenotypes in females)
i) PMID: 31279343- Novel heterozygous missense variant in HFM1 (c.3470G > A) in the proband and her mother both affected by POI. Minigene splicing assay of the WT and MT constructs revealed that an alternative splicing process were produced with the c.3470G > A variant in mRNA level.

ii) PMID: 35881270- novel compound heterozygous variants,c.1978-2A > C and c.2680 + 3_2680 + 4delAT, in two sisters with diminished ovarian reserve and recurrent pregnancy loss (RPL) in natural pregnancy and in vitro fertilization-embryo transfer (IVF-ET). Minigene assay showed that both variants could produce alternative transcripts compared to wild-type counterparts, which might result in protein dysfunction. These results demonstrated that RPL caused by the HFM1 gene might be inherited in AR mode,

iii) PMID: 36864181- novel homozygous splicing variant in HFM1 (NM_001017975.6: c.1730-1G > T) in two siblings - female with poor ovarian response and recurrent implantation failure and male with NOA. Minigene assay demonstrated that splicing variants caused abnormal alternative splicing of HFM1. For the sister, she experienced embryo arrest 9 weeks after pregnancy after undergoing 5 cycles of ART.

iv) PMID: 39929154- reported compound heterozygous variants c.1978-2A>C and c.2681-3T>A in a case of POI with unique genital characteristics; also their lit review showed that previous studies have linked HFM1 gene variants to clinical manifestations such as POI, diminished ovarian reserve, recurrent pregnancy loss, and poor outcomes in in vitro fertilization-embryo transfer.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.25 HFM1 Jasmine Chew gene: HFM1 was added
gene: HFM1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: HFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HFM1 were set to 24597873; 31279343; 35881270; 36864181; 39929154
Phenotypes for gene: HFM1 were set to Premature ovarian failure 9, MIM# 615724
Review for gene: HFM1 was set to GREEN
Added comment: Literature in OMIM- PMID:24597873- compound heterozygous variants in a familial case and an unrelated individual with primary ovarian failure

New papers (single family with monoallelic variant and expansion of phenotypes)
i) PMID: 31279343- Novel heterozygous missense variant in HFM1 (c.3470G > A) in the proband and her mother both affected by POI. Minigene splicing assay of the WT and MT constructs revealed that an alternative splicing process were produced with the c.3470G > A variant in mRNA level.

ii) PMID: 35881270- novel compound heterozygous variants,c.1978-2A > C and c.2680 + 3_2680 + 4delAT, in two sisters with diminished ovarian reserve and recurrent pregnancy loss (RPL) in natural pregnancy and in vitro fertilization-embryo transfer (IVF-ET). Minigene assay showed that both variants could produce alternative transcripts compared to wild-type counterparts, which might result in protein dysfunction. These results demonstrated that RPL caused by the HFM1 gene might be inherited in AR mode,

iii) PMID: 36864181 (2023)- novel homozygous splicing variant in HFM1 (NM_001017975.6: c.1730-1G > T) in two siblings - female with poor ovarian response and recurrent implantation failure and male with NOA. Minigene assay demonstrated that splicing variants caused abnormal alternative splicing of HFM1. For the sister, she experienced embryo arrest 9 weeks after pregnancy after undergoing 5 cycles of ART.

iv) PMID: 39929154 (2025)- reported compound heterozygous variants c.1978-2A>C and c.2681-3T>A in a case of POI with unique genital characteristics; also their lit review showed that previous studies have linked HFM1 gene variants to clinical manifestations such as POI, diminished ovarian reserve, recurrent pregnancy loss, and poor outcomes in in vitro fertilization-embryo transfer.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.25 MCM8 Zornitza Stark Marked gene: MCM8 as ready
Infertility and Recurrent Pregnancy Loss v0.25 MCM8 Zornitza Stark Gene: mcm8 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.25 MCM8 Zornitza Stark Classified gene: MCM8 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.25 MCM8 Zornitza Stark Gene: mcm8 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.24 GGN Zornitza Stark Marked gene: GGN as ready
Infertility and Recurrent Pregnancy Loss v0.24 GGN Zornitza Stark Gene: ggn has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.24 GGN Zornitza Stark Mode of pathogenicity for gene: GGN was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Infertility and Recurrent Pregnancy Loss v0.23 GGN Zornitza Stark Classified gene: GGN as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.23 GGN Zornitza Stark Gene: ggn has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.22 FKBP6 Zornitza Stark Marked gene: FKBP6 as ready
Infertility and Recurrent Pregnancy Loss v0.22 FKBP6 Zornitza Stark Gene: fkbp6 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.22 FKBP6 Zornitza Stark Classified gene: FKBP6 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.22 FKBP6 Zornitza Stark Gene: fkbp6 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.21 EIF4ENIF1 Zornitza Stark Marked gene: EIF4ENIF1 as ready
Infertility and Recurrent Pregnancy Loss v0.21 EIF4ENIF1 Zornitza Stark Gene: eif4enif1 has been classified as Green List (High Evidence).
Mendeliome v1.2435 EIF4ENIF1 Zornitza Stark Publications for gene: EIF4ENIF1 were set to 31810472; 23902945; 33095795
Mendeliome v1.2434 EIF4ENIF1 Zornitza Stark Classified gene: EIF4ENIF1 as Green List (high evidence)
Mendeliome v1.2434 EIF4ENIF1 Zornitza Stark Gene: eif4enif1 has been classified as Green List (High Evidence).
Mendeliome v1.2433 EIF4ENIF1 Zornitza Stark reviewed gene: EIF4ENIF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23902945, 39827467, 36030004, 38604507, 31810472, 33095795; Phenotypes: Primary ovarian insufficiency, MONDO:0005387, EIF4ENIF1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.344 EIF4ENIF1 Zornitza Stark Publications for gene: EIF4ENIF1 were set to 31810472; 23902945; 33095795
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.343 EIF4ENIF1 Zornitza Stark Classified gene: EIF4ENIF1 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.343 EIF4ENIF1 Zornitza Stark Gene: eif4enif1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.342 EIF4ENIF1 Zornitza Stark reviewed gene: EIF4ENIF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23902945, 39827467, 36030004, 38604507, 31810472, 33095795; Phenotypes: Primary ovarian insufficiency, MONDO:0005387, EIF4ENIF1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v0.21 EIF4ENIF1 Zornitza Stark Classified gene: EIF4ENIF1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.21 EIF4ENIF1 Zornitza Stark Gene: eif4enif1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.20 DPY19L2 Zornitza Stark Marked gene: DPY19L2 as ready
Infertility and Recurrent Pregnancy Loss v0.20 DPY19L2 Zornitza Stark Gene: dpy19l2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.20 DPY19L2 Zornitza Stark Classified gene: DPY19L2 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.20 DPY19L2 Zornitza Stark Gene: dpy19l2 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.19 MCM8 Jasmine Chew edited their review of gene: MCM8: Changed rating: GREEN
Infertility and Recurrent Pregnancy Loss v0.19 BMP15 Zornitza Stark Marked gene: BMP15 as ready
Infertility and Recurrent Pregnancy Loss v0.19 BMP15 Zornitza Stark Gene: bmp15 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.19 BMP15 Zornitza Stark Classified gene: BMP15 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.19 BMP15 Zornitza Stark Gene: bmp15 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.18 MCM8 Jasmine Chew gene: MCM8 was added
gene: MCM8 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: MCM8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM8 were set to 25437880; 25873734; 40064807; 32048466
Phenotypes for gene: MCM8 were set to Premature ovarian failure 10, MIM# 612885; Azoospermia, MONDO:0100459
Added comment: Literature in OMIM- PMID:25437880;25873734- homozygous variants reported in affected females with premature ovarian failure, supported by functional evidence

New papers:
i) PMID: 40064807- A novel homozygous frameshift variant (p. Gly333Glufs*50) in two siblings diagnosed with primary gonadal dysgenesis from a consanguineous family. The testes tissue sections in the male showed a Sertoli cell-only syndrome (SCOS). Functional analysis in vitro suggested that the mutation results in a truncated protein of MCM8 in HEK293T cells, and immunohistochemistry in vivo showed decreased expression of MCM8 protein. This study expands the mutational spectrum of MCM8 involved in male NOA and female POI.

ii) PMID: 32048466- A novel homozygous frameshift mutation in the MCM8 gene in two affected sisters with POI. Reverse transcription polymerase chain reaction revealed that the frameshift mutation led to a remarkably reduced level of MCM8 transcript products, and chromosomal instability study showed that the ability of mutant MCM8 to repair DNA breaks was impaired.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.18 AURKC Zornitza Stark Marked gene: AURKC as ready
Infertility and Recurrent Pregnancy Loss v0.18 AURKC Zornitza Stark Gene: aurkc has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.18 AURKC Zornitza Stark Classified gene: AURKC as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.18 AURKC Zornitza Stark Gene: aurkc has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.17 NOBOX Jasmine Chew changed review comment from: Literature in OMIM- PMIM:17701902;21837770;25514101- heterozygous missense and LOF variants reported in affected women with primary ovarian insufficiency, supported by functional evidence

New papers (expansion of phenotypes and novel biallelic variants reported in POI patients)-
i. PMID: 39871066- A heterozygous missense variant (p.His617Tyr) in two European women with distinct distinct oocyte, zygote, and embryo maturation arrest (OZEMA) phenotype. The same variant has been observed in other two woman experiencing embryonic developmental arrest from the database of Juno Genetics. Given that all affected women have a normal to high ovarian reserve, a typical POI phenotype can be excluded in these cases.

ii. PMID: 34480423- novel compound heterozygous truncating variants (p.Arg276Ter and p.Gly474AlafsTer76) in a Belgian patient presenting POI

iii. PMID: 29067606- novel homozygous c.1489delT variant in two sisters with POI
Sources: Literature; to: Literature in OMIM- PMIM:17701902;21837770;25514101- heterozygous missense and LOF variants reported in affected women with primary ovarian insufficiency, supported by functional evidence

New papers (expansion of phenotypes and novel biallelic variants reported in POI patients)-
i. PMID: 39871066- A heterozygous missense variant (p.His617Tyr) in two European women with distinct distinct oocyte, zygote, and embryo maturation arrest (OZEMA) phenotype. The same variant has been observed in other two woman experiencing embryonic developmental arrest from the database of Juno Genetics. Given that all affected women have a normal to high ovarian reserve, a typical POI phenotype can be excluded in these cases.

ii. PMID: 34480423- Novel compound heterozygous truncating variants (p.Arg276Ter and p.Gly474AlafsTer76) in a Belgian patient presenting POI.

iii. PMID: 29067606- a novel homozygous c.1489delT variant in two sisters with POI
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.17 NOBOX Jasmine Chew gene: NOBOX was added
gene: NOBOX was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: NOBOX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NOBOX were set to 17701902; 21837770; 25514101; 39871066; 34480423; 29067606
Phenotypes for gene: NOBOX were set to Premature ovarian failure 5, MIM# 611548
Review for gene: NOBOX was set to GREEN
Added comment: Literature in OMIM- PMIM:17701902;21837770;25514101- heterozygous missense and LOF variants reported in affected women with primary ovarian insufficiency, supported by functional evidence

New papers (expansion of phenotypes and novel biallelic variants reported in POI patients)-
i. PMID: 39871066- A heterozygous missense variant (p.His617Tyr) in two European women with distinct distinct oocyte, zygote, and embryo maturation arrest (OZEMA) phenotype. The same variant has been observed in other two woman experiencing embryonic developmental arrest from the database of Juno Genetics. Given that all affected women have a normal to high ovarian reserve, a typical POI phenotype can be excluded in these cases.

ii. PMID: 34480423- novel compound heterozygous truncating variants (p.Arg276Ter and p.Gly474AlafsTer76) in a Belgian patient presenting POI

iii. PMID: 29067606- novel homozygous c.1489delT variant in two sisters with POI
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.17 PATL2 Jasmine Chew changed review comment from: Literature in OMIM- PMID:28965844;28965849; 35091966- biallelic variants in affected women with infertility due to oocyte maturation arrest

New papers-
i) PMID: 32048119- two novel homozygous missense variants (p.Pro510Thr and p.Ser459Tyr) in three patients from two consanguineous families with female infertility due to oocyte maturation arrest. Western immunoblotting analysis showed that the expression levels of the two novel mutant PATL2 proteins decreased significantly.

ii) PMID: 30765866- four novel homozygous missense variants (p.V260M, p.Q300*, p.T425P, and p.D293Y), a novel frameshift variant (p.N239Tfs*9), and a reported splicing mutation (p.R75Vfs*21) in PATL2 in seven affected individuals from five unrelated families, showing a multiplicity of phenotypes in oocyte maturation arrest, fertilization failure, or embryonic developmental arrest.

iii) PMID: 39476306- novel compound heterozygous splicing variant (c.516-1G > T and c.877-1G > A) in a woman with oocyte degeneration and fertilization failure. Minigene splicing assays revealed that the c.516-1G > T resulted in a deletion of 8 bases in mRNA that causes a frameshift (p.P173Q fs*13) and the c.877-1G > A led to the skipping of exons 10 and 11 and retention of introns 8-9 in PATL2 mRNA.

iv) PMID: 38536595- 15 novel biallelic variants in 18 families with impaired oocyte maturation, fertilization problems, embryonic arrest, or implantation failure
Sources: Literature; to: Literature in OMIM- PMID:28965844;28965849; 35091966- biallelic variants in affected women with infertility due to oocyte maturation arrest

New papers-
i) PMID: 32048119- two novel homozygous missense variants (p.Pro510Thr and p.Ser459Tyr) in three patients from two consanguineous families with female infertility due to oocyte maturation arrest. Western immunoblotting analysis showed that the expression levels of the two novel mutant PATL2 proteins decreased significantly.

ii) PMID: 30765866- four novel homozygous missense variants (p.V260M, p.Q300*, p.T425P, and p.D293Y), a novel frameshift variant (p.N239Tfs*9), and a reported splicing mutation (p.R75Vfs*21) in PATL2 in seven affected individuals from five unrelated families, showing a multiplicity of phenotypes in oocyte maturation arrest, fertilization failure, or embryonic developmental arrest.

iii) PMID: 39476306- novel compound heterozygous splicing variant (c.516-1G > T and c.877-1G > A) in a woman with oocyte degeneration and fertilization failure. Minigene splicing assays revealed that the c.516-1G > T resulted in a deletion of 8 bases in mRNA that causes a frameshift (p.P173Q fs*13) and the c.877-1G > A led to the skipping of exons 10 and 11 and retention of introns 8-9 in PATL2 mRNA.

iv) PMID: 38536595- 15 novel biallelic variants in 18 families with infertile women with IVF/ICSI failure due to impaired oocyte maturation, fertilization problems, embryonic arrest, or implantation failure.
Sources: Literature
Prepair 1000+ v1.1826 FITM2 Melanie Marty edited their review of gene: FITM2: Changed publications: 28067622, 30214770, 30288795, 35754111
Infertility and Recurrent Pregnancy Loss v0.17 PATL2 Jasmine Chew gene: PATL2 was added
gene: PATL2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: PATL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PATL2 were set to 28965844; 28965849; 35091966; 32048119; 30765866; 39476306; 38536595
Phenotypes for gene: PATL2 were set to Oocyte maturation defect 4, MIM# 617743
Review for gene: PATL2 was set to GREEN
Added comment: Literature in OMIM- PMID:28965844;28965849; 35091966- biallelic variants in affected women with infertility due to oocyte maturation arrest

New papers-
i) PMID: 32048119- two novel homozygous missense variants (p.Pro510Thr and p.Ser459Tyr) in three patients from two consanguineous families with female infertility due to oocyte maturation arrest. Western immunoblotting analysis showed that the expression levels of the two novel mutant PATL2 proteins decreased significantly.

ii) PMID: 30765866- four novel homozygous missense variants (p.V260M, p.Q300*, p.T425P, and p.D293Y), a novel frameshift variant (p.N239Tfs*9), and a reported splicing mutation (p.R75Vfs*21) in PATL2 in seven affected individuals from five unrelated families, showing a multiplicity of phenotypes in oocyte maturation arrest, fertilization failure, or embryonic developmental arrest.

iii) PMID: 39476306- novel compound heterozygous splicing variant (c.516-1G > T and c.877-1G > A) in a woman with oocyte degeneration and fertilization failure. Minigene splicing assays revealed that the c.516-1G > T resulted in a deletion of 8 bases in mRNA that causes a frameshift (p.P173Q fs*13) and the c.877-1G > A led to the skipping of exons 10 and 11 and retention of introns 8-9 in PATL2 mRNA.

iv) PMID: 38536595- 15 novel biallelic variants in 18 families with impaired oocyte maturation, fertilization problems, embryonic arrest, or implantation failure
Sources: Literature
Prepair 1000+ v1.1826 FITM2 Melanie Marty reviewed gene: FITM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28067622, 30214770, 30288795, 28067622, 35754111; Phenotypes: Siddiqi syndrome, MIM#618635; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1826 ABCB11 Melanie Marty reviewed gene: ABCB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 16871584, 23141890, 9806540, 15300568, 11172067; Phenotypes: Cholestasis, progressive familial intrahepatic 2, MIM# 601847, Cholestasis, benign recurrent intrahepatic, 2, MIM# 605479; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1826 SLC1A4 Melanie Marty reviewed gene: SLC1A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25930971, 26138499, 26041762, 27193218, 29989513; Phenotypes: Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1826 SETX Melanie Marty reviewed gene: SETX: Rating: GREEN; Mode of pathogenicity: None; Publications: 23129421; Phenotypes: Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (MIM#606002); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1826 RPGRIP1L Melanie Marty reviewed gene: RPGRIP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 17558409, 17558407, 17960139, 26071364, 19574260, 29991045; Phenotypes: Joubert syndrome 7, MIM# 611560, Meckel syndrome 5, MIM# 611561, COACH syndrome 3, MIM# 619113, Ciliopathy, RPGRIP1L-related, MONDO:0005308; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.17 POF1B Jasmine Chew changed review comment from: Literature in OMIM- PMID:16773570- familial case with POF carrying homozygous R329Q, supported by functional evidence.

New papers:
i) PMID: 25676666- reciprocal translocation between chromosomes X and 3 and an additional heterozygous missense variant p.Arg329Gln in a POI case, which explains the phenotype. Functional analysis of the POF1B variant p.Arg329Gln showed diminished binding of the mutant protein to non-muscle actin, and the authors hypothesized a possible role for POF1B in pairing of meiotic chromosomes or as an anti-apoptotic factor.

ii) PMID: 34423420- novel homozygous missense variant p.K311T in a Chinese patient with POF, adjacent to the known p.R329Q variant, suggesting that would damage the capacity of POF1B to bind non-muscle actin filaments.

iii) PMID: 34707299 - homozygous missense variant p.(Arg329Gln) in a female with POI (identical to PMID:16773570).
Sources: Literature; to: Literature in OMIM- PMID:16773570- familial case with POF carrying homozygous missense variant R329Q, supported by functional evidence.

New papers:
i) PMID: 25676666- reciprocal translocation between chromosomes X and 3 and an additional heterozygous missense variant p.Arg329Gln in a POI case, which explains the phenotype. Functional analysis of the POF1B variant p.Arg329Gln showed diminished binding of the mutant protein to non-muscle actin, and the authors hypothesized a possible role for POF1B in pairing of meiotic chromosomes or as an anti-apoptotic factor.

ii) PMID: 34423420- novel homozygous missense variant p.K311T in a Chinese patient with POF, adjacent to the known p.R329Q variant, suggesting that would damage the capacity of POF1B to bind non-muscle actin filaments.

iii) PMID: 34707299 - homozygous missense variant p.(Arg329Gln) in a female with POI (identical to PMID:16773570).
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.17 POF1B Jasmine Chew changed review comment from: Literature in OMIM- PMID:16773570- familial case with POF carrying homozygous R329Q, supported by functional evidence.

New papers:
i) PMID: 25676666- reciprocal translocation between chromosomes X and 3 and an additional heterozygous missense variant p.Arg329Gln in a POI case, which explains the phenotype. Functional analysis of the POF1B variant p.Arg329Gln showed diminished binding of the mutant protein to non-muscle actin, and the authors hypothesized a possible role for POF1B in pairing of meiotic chromosomes or as an anti-apoptotic factor.

ii) PMID: 34423420- novel homozygous missense variant p.K311T in a Chinese patient with POF, adjacent to the known p.R329Q variant, suggesting that would damage the capacity of POF1B to bind non-muscle actin filaments.

iii) PMID: 34707299 - homozygous missense variant p.(Arg329Gln) in a female with POI (identical to PMID:16773570).
Sources: Literature; to: Literature in OMIM- PMID:16773570- familial case with POF carrying homozygous R329Q, supported by functional evidence.

New papers:
i) PMID: 25676666- reciprocal translocation between chromosomes X and 3 and an additional heterozygous missense variant p.Arg329Gln in a POI case, which explains the phenotype. Functional analysis of the POF1B variant p.Arg329Gln showed diminished binding of the mutant protein to non-muscle actin, and the authors hypothesized a possible role for POF1B in pairing of meiotic chromosomes or as an anti-apoptotic factor.

ii) PMID: 34423420- novel homozygous missense variant p.K311T in a Chinese patient with POF, adjacent to the known p.R329Q variant, suggesting that would damage the capacity of POF1B to bind non-muscle actin filaments.

iii) PMID: 34707299 - homozygous missense variant p.(Arg329Gln) in a female with POI (identical to PMID:16773570).
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.17 POF1B Jasmine Chew gene: POF1B was added
gene: POF1B was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: POF1B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: POF1B were set to 16773570; 34707299; 25676666; 34423420
Phenotypes for gene: POF1B were set to Premature ovarian failure 2B, MIM# 300604
Review for gene: POF1B was set to GREEN
Added comment: Literature in OMIM- PMID:16773570- familial case with POF carrying homozygous R329Q, supported by functional evidence.

New papers:
i) PMID: 25676666- reciprocal translocation between chromosomes X and 3 and an additional heterozygous missense variant p.Arg329Gln in a POI case, which explains the phenotype. Functional analysis of the POF1B variant p.Arg329Gln showed diminished binding of the mutant protein to non-muscle actin, and the authors hypothesized a possible role for POF1B in pairing of meiotic chromosomes or as an anti-apoptotic factor.

ii) PMID: 34423420- novel homozygous missense variant p.K311T in a Chinese patient with POF, adjacent to the known p.R329Q variant, suggesting that would damage the capacity of POF1B to bind non-muscle actin filaments.

iii) PMID: 34707299 - homozygous missense variant p.(Arg329Gln) in a female with POI (identical to PMID:16773570).
Sources: Literature
Prepair 1000+ v1.1826 RAD50 Melanie Marty reviewed gene: RAD50: Rating: GREEN; Mode of pathogenicity: None; Publications: 19409520, 32212377, 33378670; Phenotypes: Nijmegen breakage syndrome-like disorder, MIM# 613078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.17 PRDM9 Jasmine Chew gene: PRDM9 was added
gene: PRDM9 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: PRDM9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM9 were set to 34257419
Phenotypes for gene: PRDM9 were set to Primary ovarian insufficiency, MONDO:0005387
Review for gene: PRDM9 was set to GREEN
Added comment: i) PMID: 34257419 (2021): 3 heterozygous variants in 4 unrelated premature ovarian insufficiency (POI) patients (P1,2- p.Arg77*, P3- p.Lys226Met, P4- p.Ile213Ser); All mutant proven to affect the H3K4 methyltransferase activity of the protein and more apoptotic oocytes were observed in Prdm9+/- mice ovaries indicating the heterozygous knockout oocytes were more susceptible to exogenous stress.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.17 PSMC3IP Jasmine Chew gene: PSMC3IP was added
gene: PSMC3IP was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: PSMC3IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMC3IP were set to 21963259; 35352317; 34878148; 30406445; 29240891
Phenotypes for gene: PSMC3IP were set to Ovarian dysgenesis 3, MIM# 614324
Review for gene: PSMC3IP was set to GREEN
Added comment: Literature in OMIM- PMID:21963259

New papers (new variants reported)- PMID:35352317; 34878148; 30406445; 29240891 (Supported by functional evidence in 25820426)
Sources: Literature
Prepair 1000+ v1.1826 RAB27A Melanie Marty reviewed gene: RAB27A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32374962, 32107531; Phenotypes: Griscelli syndrome, type 2, MIM# 607624; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1826 QDPR Melanie Marty reviewed gene: QDPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 11153907; Phenotypes: Hyperphenylalaninemia, BH4-deficient, C, MIM# 261630; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1826 PUS1 Melanie Marty reviewed gene: PUS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25227147, 17056637, 15108122, 32287105, 31641589, 28832011; Phenotypes: Myopathy, lactic acidosis, and sideroblastic anemia 1, MIM# 600462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1826 PRX Melanie Marty reviewed gene: PRX: Rating: GREEN; Mode of pathogenicity: None; Publications: 11133365, 11157804, 15197604, 21079185, 22847150, 10839370, 32460404, 31523542, 31426691; Phenotypes: Charcot-Marie-Tooth disease, type 4F, MIM# 614895, Dejerine-Sottas disease, MIM# 145900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.17 SOHLH1 Jasmine Chew gene: SOHLH1 was added
gene: SOHLH1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: SOHLH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SOHLH1 were set to 25774885; 20506135; 28718531; 38448741; 34448846
Phenotypes for gene: SOHLH1 were set to Ovarian dysgenesis 5, MIM #617690; Spermatogenic failure 32, MIM #618115
Review for gene: SOHLH1 was set to GREEN
Added comment: Literature in OMIM- PMID:25774885; 20506135; 28718531

New papers for ovarian dysgenesis:
i) PMID: 38448741- novel homozygous missense variant (Ser92Leu) in three affected females from an inbred Mexican family with familial ovarian dysgenesis. Histological examination showed ovarian cortex marked by fibrosis and an almost complete absence of follicle, which was consistent with the findings in the gonads of Sohlh1-deficient mice (PMID: 16690745).

New papers for spermatogenic failure (new recessive-inheritance pattern of SOHLH1-associated male infertility):
i) PMID: 34448846- homozygous c.346-1G > A variant in a severe oligozoospermia (SOZ) patient, characterized with severely decreased sperm count. The homozygous variant leads to the sharp decrease in various germ cells and spermatogenesis dysfunction, which is similar to the phenotype of SOHLH1 knockout male mice (PMID: 30614095). Suggested that previously reported heterozygous c.346-1G > A variant is associated with teratozoospermia but not a direct cause for NOA and the homozygous c.346-1G > A variant impairs spermatogenesis and further leads to the reduced sperm count, eventually causing male infertility.
Sources: Literature
Prepair 1000+ v1.1826 PRDM12 Melanie Marty reviewed gene: PRDM12: Rating: GREEN; Mode of pathogenicity: None; Publications: 26005867, 33789102, 33010785, 32828702; Phenotypes: Neuropathy, hereditary sensory and autonomic, type VIII, MIM# 616488; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.17 BMP15 Jasmine Chew gene: BMP15 was added
gene: BMP15 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: BMP15 was set to Other
Publications for gene: BMP15 were set to 15136966; 16508750; 16464940; 19263482; 39850788; 35861920
Phenotypes for gene: BMP15 were set to Ovarian dysgenesis 2, MIM# 300510; Premature ovarian failure 4, MIM# 300510
Review for gene: BMP15 was set to GREEN
Added comment: Literature in OMIM (PMID: 15136966;16508750;16464940;19263482)- multiple affected females carrying monoallelic variants with POI+/- ovarian dysgenesis.

New papers reporting on biallelic variants in affected females:
i) PMID: 39850788- novel homozygous variant (p.C320Y) in 2 Palestinian sisters born to consanguineous parents with ovarian dysgenesis and primary amenorrhea; in-vitro assay also showed decreased in BMP signaling in cells expressing the homozygous BMP15 mutant when compared to the WT control.
ii) PMID: 35861920- novel compound heterozygous variant (p. R264Q and p. P359L) in two siblings with POI. Both missense variants reduced the level of the BMP15 protein and impaired the function of BMP15 in promoting granulosa cell proliferation in vitro.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.17 EIF4ENIF1 Jasmine Chew edited their review of gene: EIF4ENIF1: Changed rating: GREEN
Infertility and Recurrent Pregnancy Loss v0.17 EIF4ENIF1 Jasmine Chew gene: EIF4ENIF1 was added
gene: EIF4ENIF1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: EIF4ENIF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF4ENIF1 were set to 23902945; 39827467; 36030004; 38604507; 31810472; 33095795
Phenotypes for gene: EIF4ENIF1 were set to Primary ovarian insufficiency, MONDO:0005387, EIF4ENIF1-related
Added comment: i) PMID: 23902945- heterozygous stop gained p. Ser429X variant in 6 POI-affected women segregated in a large family; mRNA in white blood cells from 3 affected women demonstrated nonsense mutant transcript at a decreased proportion compared with that in gDNA, suggesting haploinsufficiency or dominant negative effect. A stop-gain mouse model was created for the heterozygous variant by PMID: 39827467 (2025), which replicated POI phenotype in women (i.e., decreased reproductive lifespan and early oocyte loss).

ii) PMID: 36030004 - two variants, p.R4del and (p.G954A in two sporadic Han Chinese POI patients. Western blot analysis further demonstrated that both of the two variants exhibited reduced mRNA and protein expression levels compared with the wild-type in vitro

iii) PMID: 38604507 - novel missense variant (p.R208H) in a patient with POI and in vitro transfection study showed that overexpression R208H significantly (P < 0.0001) lowered the overall translation efficiency, whereas exhibiting a reduced translation inhibitory effect on high-TE genes (TE > 2 in GFP control group).
Sources: Literature
Prepair 1000+ v1.1826 VPS33B Michelle Torres reviewed gene: VPS33B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31479177, 30561130, 28017832; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 1 MIM#208085, Cholestasis, progressive familial intrahepatic, 12 MIM#620010, Keratoderma-ichthyosis-deafness syndrome, autosomal recessive MIM#620009; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.17 SYCP3 Jasmine Chew edited their review of gene: SYCP3: Changed rating: GREEN
Infertility and Recurrent Pregnancy Loss v0.17 KHDC3L Jasmine Chew edited their review of gene: KHDC3L: Changed rating: GREEN
Prepair 1000+ v1.1826 PPA2 Melanie Marty reviewed gene: PPA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27523598, 34400813; Phenotypes: Sudden cardiac failure, infantile, MIM#617222, Sudden cardiac failure, alcohol-induced, MIM#617223; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.17 ZP1 Jasmine Chew gene: ZP1 was added
gene: ZP1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: ZP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZP1 were set to 24670168; 30810869; 36385415; 39380244; 36529558
Phenotypes for gene: ZP1 were set to Oocyte/zygote/embryo maturation arrest 1, MIM# 615774
Review for gene: ZP1 was set to GREEN
Added comment: Literature in OMIM (PMID: 24670168;30810869)- familial cases with homozygous missense/frameshift variant in affected women with primary infertility due to oocyte maturation defect; supported by functional evidence.

New papers:
i) PMID: 36385415- homozygous nonsense variant p.Gln210Ter in a case with primary infertility (C19)

ii) PMID: 39380244;36529558- homozygous missense variants in the same AA position (p.Arg366Trp and p.Arg366Gln) in unrelated females with with empty follicle syndrome; supported by functional evidence
Sources: Literature
Prepair 1000+ v1.1826 POC1A Melanie Marty reviewed gene: POC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 22840364, 22840363, 26374189, 26162852, 26791357; Phenotypes: Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM# 614813; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.17 ZP2 Jasmine Chew gene: ZP2 was added
gene: ZP2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: ZP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZP2 were set to 29895852; 30810869; 39443359; 33604805
Phenotypes for gene: ZP2 were set to Oocyte/zygote/embryo maturation arrest 6, MIM# 618353
Added comment: Literature in OMIM (PMID: 29895852; 30810869)- familial cases with homozygous variants (splice and missense) reported in affected women with defective/absent oocyte zona pellucida, supported by functional evidence

New papers-
i) PMID: 39443359- novel compound heterozygous variant (c.1924C > T and c.1695-2A > G) in a Chinese Han family with primary female infertility due to oocyte degeneration caused by absent/thin ZP; both variants (c.1924C > T and c.1695-2A > G) resulted in truncated ZP2 proteins (p.R642X and p.C566Hfs*2) that lost the transmembrane domain, which prevented the secretion of the mutant ZP2 proteins and produced a structurally abnormal ZP.

ii) PMID: 33604805- novel homozygous frameshift variant (p.Q412Rfs*17) in two infertile sisters in a family with a thin zona pellucida (ZP) phenotype, supported by functional evidence.
Sources: Literature
Prepair 1000+ v1.1826 PGAP1 Melanie Marty reviewed gene: PGAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 24784135, 25823418, 25804403, 26050939; Phenotypes: Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities, MIM# 615802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1826 PEX7 Melanie Marty reviewed gene: PEX7: Rating: GREEN; Mode of pathogenicity: None; Publications: 11781871, 12522768, 12325024; Phenotypes: Peroxisome biogenesis disorder 9B, MIM# 614879, Rhizomelic chondrodysplasia punctata, type 1, MIM# 215100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1826 TCIRG1 Michelle Torres reviewed gene: TCIRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34624559, 34210262, 30084437, 28816234; Phenotypes: Osteopetrosis, autosomal recessive 1 MIM#259700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1826 LRSAM1 Melanie Marty changed review comment from: Only a single family reported with recessive inheritance.

Over 30 families reported with dominant disease.

Age of onset typically between the second and fifth decades of life.

Marking as red for carrier screening due to age of onset and limited evidence for recessive disease.; to: Only a single family reported with recessive inheritance.

Over 30 families reported with dominant disease.

Age of onset typically between the second and fifth decades of life. Peak age of onset in second decade (range childhood to 76 years) (OMIM).

Marking as red for carrier screening due to age of onset and limited evidence for recessive disease.
Prepair 1000+ v1.1826 LRSAM1 Melanie Marty changed review comment from: Only a single family reported with recessive inheritance.

Over 30 families reported with dominant disease.

Age of onset typically between the second and fifth decades of life.; to: Only a single family reported with recessive inheritance.

Over 30 families reported with dominant disease.

Age of onset typically between the second and fifth decades of life.

Marking as red for carrier screening due to age of onset and limited evidence for recessive disease.
Prepair 1000+ v1.1826 LRSAM1 Melanie Marty edited their review of gene: LRSAM1: Changed publications: 38330802, 33568173
Prepair 1000+ v1.1826 TBC1D23 Michelle Torres reviewed gene: TBC1D23: Rating: GREEN; Mode of pathogenicity: None; Publications: 28823707, 28823706; Phenotypes: Pontocerebellar hypoplasia, type 11 MIM#617695; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.17 TACC3 Jasmine Chew edited their review of gene: TACC3: Changed phenotypes: Female infertility due to oocyte meiotic arrest, MONDO:0044626
Infertility and Recurrent Pregnancy Loss v0.17 TACC3 Jasmine Chew changed review comment from: PMID: 36395215- compound heterozygous variants (Patient 1- p.Ser177Thr/p.Pro395Arg, Patient 2- p.Lys225_Cys236del/p.Gly631Val) in two unrelated females presented with oocyte maturation arrest and undetectable spindles on both polarization and fluorescence microscopy. Their oocytes lacked huoMTOCs and had poorly organized microtubules, similar to the phenotype of TACC3 depletion in vitro, which suggests a loss-of-function mechanism causing oocyte maturation arrest and infertility.

Note: couldn't access MONDO # as website down (phenotypes to be updated); to: PMID: 36395215- compound heterozygous variants (Patient 1- p.Ser177Thr/p.Pro395Arg, Patient 2- p.Lys225_Cys236del/p.Gly631Val) in two unrelated females presented with oocyte maturation arrest and undetectable spindles on both polarization and fluorescence microscopy. Their oocytes lacked huoMTOCs and had poorly organized microtubules, similar to the phenotype of TACC3 depletion in vitro, which suggests a loss-of-function mechanism causing oocyte maturation arrest and infertility.
Prepair 1000+ v1.1826 SRD5A3 Michelle Torres reviewed gene: SRD5A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32424323, 20301507; Phenotypes: Congenital disorder of glycosylation, type Iq MIM#612379, Kahrizi syndrome#612713, SRD5A3-congenital disorder of glycosylation (MONDO:0012885); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.17 ZP3 Jasmine Chew gene: ZP3 was added
gene: ZP3 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: ZP3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ZP3 were set to 28886344; 30810869; 39932488; 37908588
Phenotypes for gene: ZP3 were set to Oocyte/zygote/embryo maturation arrest 3, MIM# 617712
Review for gene: ZP3 was set to GREEN
Added comment: Literature in OMIM (PMID: 28886344;30810869)- familial cases with heterozygous missense variants supported by functional evidence (dominant-negative effect).

New papers-
i) PMID: 39932488- 4 heterozygous missense variants (2 novel, 2 known) with primary infertility, characterized by zona pellucida abnormalities or abnormal oocyte morphology. Also quoted that "To date, no studies have reported successful pregnancies in patients with ZP3 variants, suggesting that ZP3 plays an indispensable role in zona pellucida assembly and that ZP3 deficiency currently has no effective solution."

ii) PMID: 37908588- novel homozygous missense variant in a female with empty follicle syndrome (EFS), who failed to retrieve any oocytes after three rounds of ovarian stimulation despite the presence of large follicles.
Sources: Literature
Prepair 1000+ v1.1826 SLC39A8 Michelle Torres reviewed gene: SLC39A8: Rating: GREEN; Mode of pathogenicity: None; Publications: 37023243, 26637978, 26637979, 29453449; Phenotypes: Congenital disorder of glycosylation, type IIn MIM#616721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.17 TUBB8 Jasmine Chew gene: TUBB8 was added
gene: TUBB8 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: TUBB8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TUBB8 were set to 26789871; 27273344; 33970371; 39834092
Phenotypes for gene: TUBB8 were set to Oocyte/zygote/embryo maturation arrest 2, MIM# 616780
Review for gene: TUBB8 was set to GREEN
Added comment: Literature from OMIM (PMID: 26789871;27273344)- multiple familial cases and supporting functional evidence (monoallelic- dominant-negative effect; biallelic- functionally null, disrupt spindle assembly and cause abnormalities in oocyte maturation, fertilization, and embryonic development)

More recent supporting evidence-
i) PMID: 39834092- functional evidence elucidating how TUBB8 missense variants cause oocyte maturation arrest
ii) PMID: 33970371- 29 variants in TUBB8 from 32 independent families with female infertility, of which 20 were novel, expanding the variant spectrum of TUBB8 (i.e., extremely involved in complete cleavage failure and embryonic arrest)
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.17 AURKC Jasmine Chew gene: AURKC was added
gene: AURKC was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: AURKC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AURKC were set to 17435757; 19147683; 21733974
Phenotypes for gene: AURKC were set to Spermatogenic failure 5, MIM #243060
Review for gene: AURKC was set to GREEN
Added comment: i) PMID: 17435757- homozygous 1bp del (c.144delC; 603495.0001) in 10 infertile men (4 were unrelated French citizens of African descent) with a large-headed sperm phenotype, which resulted in premature termination of translation, yielding a truncated protein that lacks the kinase domain
ii) PMID: 19147683 - homozygous c.144delC found in 31 patients and compound heterozygous for c.144delC and a missense variant (C229Y) in 30 patients with large-headed spermatozoa

iii) PMID: 21733974- compound heterozygous for the c.144delC variant and a splice variant ((c.436-2A-G; predicted to cause skipping of exon 5) in 2 infertile brothers of Tunisian descent with macrozoospermia and a younger sister who had yet tried to achieve pregnancy
Sources: Literature
Mendeliome v1.2433 CDC20 Zornitza Stark Marked gene: CDC20 as ready
Mendeliome v1.2433 CDC20 Zornitza Stark Gene: cdc20 has been classified as Green List (High Evidence).
Mendeliome v1.2433 CDC20 Zornitza Stark Classified gene: CDC20 as Green List (high evidence)
Mendeliome v1.2433 CDC20 Zornitza Stark Gene: cdc20 has been classified as Green List (High Evidence).
Mendeliome v1.2432 CDC20 Zornitza Stark gene: CDC20 was added
gene: CDC20 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDC20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDC20 were set to 32666501; 33683667; 33898437; 34218387
Phenotypes for gene: CDC20 were set to Oocyte/zygote/embryo maturation arrest 14, MIM# 620276
Review for gene: CDC20 was set to GREEN
Added comment: i) PMID: 32666501- Biallelic (homozygous/compound heterozygous) variants in 5 unrelated Chinese women with infertility due to oocyte maturation arrest. Knocked down mouse oocytes showed an metaphase I (MI) arrest phenotype that could be rescued by injection of wildtype human CDC20 cRNA; all of the variants significantly reduced the ability of CDC20 to rescue the phenotype.

ii) PMID: 33683667- a compound heterozygous (missense and nonsense) variant in a Chinese woman with infertility due to oocyte maturation abnormalities and early embryonic arrest.

iii) PMID: 33898437- 4 patients from 3 Chinese families with homozygous or compound heterozygous variants with infertility due to oocyte maturation arrest, fertilization failure, and early embryonic arrest. Functional analysis in mouse oocytes with knockdown of Cdc20 showed that the homozygous and compound heterozygous variants significantly reduced the ability of CDC20 to rescue the lack of PB1 extrusion (MI arrest).

iv) PMID: 34218387- homozygous missense variant in a Chinese woman with infertility due to oocyte maturation arrest at MI and fertilization failure of MII oocytes.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.17 CDC20 Zornitza Stark Marked gene: CDC20 as ready
Infertility and Recurrent Pregnancy Loss v0.17 CDC20 Zornitza Stark Gene: cdc20 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.17 CDC20 Zornitza Stark Classified gene: CDC20 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.17 CDC20 Zornitza Stark Gene: cdc20 has been classified as Green List (High Evidence).
Mendeliome v1.2431 CCNB3 Zornitza Stark Marked gene: CCNB3 as ready
Mendeliome v1.2431 CCNB3 Zornitza Stark Gene: ccnb3 has been classified as Green List (High Evidence).
Mendeliome v1.2431 CCNB3 Zornitza Stark Classified gene: CCNB3 as Green List (high evidence)
Mendeliome v1.2431 CCNB3 Zornitza Stark Gene: ccnb3 has been classified as Green List (High Evidence).
Mendeliome v1.2430 CCNB3 Zornitza Stark gene: CCNB3 was added
gene: CCNB3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CCNB3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCNB3 were set to 35722368; 32938693; 34021051; 30770433; 34850816
Phenotypes for gene: CCNB3 were set to Recurrent pregnancy loss, susceptibility to, MONDO:0000144, CCNB3-related
Review for gene: CCNB3 was set to GREEN
Added comment: i) PMID: 35722368- homozygous missense variant (p.P119Q) in the female of unexplained recurrent pregnancy loss (RPL) couple (couple 29)
ii) PMID: 32938693- homozygous missense variant (p.V1251D) in two sisters with RPL and two of their POCs were characterised and found to be triploid digynic due to the failure of meiosis II.
iii) PMID: 34021051- novel homozygous frameshift variant (p.Val1321Glyfs*4, due to splicing causing exon skipping) in a patient with 16 RPL and one of her miscarriages is triploid digynic resulted from the failure of meiosis I.

Supporting mouse evidence:
iv) PMID: 30770433- Ccnb3 knockout also causes female infertility due to the failure of metaphase to anaphase transition in meiosis I and the extrusion of the first polar body. The infertility in these mice appeared to be due to embryonic lethality before embryonic day 7.5 and some of their oocytes fertilised by intracytoplasmic sperm injection led to triploid embryos.
v) PMID: 34850816- Ccnb3-deficient mouse model is similar to a human infertility condition—recurrent pregnancy loss (RPL). Their findings demonstrate that the triploidy of embryos derived from Ccnb3-deficient oocytes is the primary cause of embryo death (i.e., such embryos can be rescued with euploid nuclei, whereas cytoplasmic Ccnb3 transcript is dispensable for zygotic genome activation and embryo development).
Sources: Expert Review
Infertility and Recurrent Pregnancy Loss v0.16 CCNB3 Zornitza Stark Marked gene: CCNB3 as ready
Infertility and Recurrent Pregnancy Loss v0.16 CCNB3 Zornitza Stark Gene: ccnb3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.16 CCNB3 Zornitza Stark Phenotypes for gene: CCNB3 were changed from to Recurrent pregnancy loss, susceptibility to, MONDO:0000144, CCNB3-related
Infertility and Recurrent Pregnancy Loss v0.15 CCNB3 Zornitza Stark reviewed gene: CCNB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Recurrent pregnancy loss, susceptibility to, MONDO:0000144, CCNB3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.15 CCNB3 Zornitza Stark Classified gene: CCNB3 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.15 CCNB3 Zornitza Stark Gene: ccnb3 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.14 DMRT1 Zornitza Stark Marked gene: DMRT1 as ready
Infertility and Recurrent Pregnancy Loss v0.14 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.14 DMRT1 Zornitza Stark Phenotypes for gene: DMRT1 were changed from to Azoospermia, MONDO:0100459, DMRT1-related
Infertility and Recurrent Pregnancy Loss v0.13 DMRT1 Zornitza Stark Classified gene: DMRT1 as Amber List (moderate evidence)
Infertility and Recurrent Pregnancy Loss v0.13 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Amber List (Moderate Evidence).
Infertility and Recurrent Pregnancy Loss v0.12 DMRT1 Zornitza Stark commented on gene: DMRT1: Rare variants enriched in azoospermia cohorts. However, variants are missense, pathogenicity more difficult to determine in the absence of segregation or other data.
Infertility and Recurrent Pregnancy Loss v0.12 DMRT1 Zornitza Stark reviewed gene: DMRT1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Azoospermia, MONDO:0100459, DMRT1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.1826 WDR35 Zornitza Stark Marked gene: WDR35 as ready
Prepair 1000+ v1.1826 WDR35 Zornitza Stark Gene: wdr35 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1826 WDR35 Zornitza Stark Phenotypes for gene: WDR35 were changed from Short-rib thoracic dysplasia 7 with or without polydactyly, 614091 (3) to Cranioectodermal dysplasia 2 MIM#613610; Short-rib thoracic dysplasia 7 with or without polydactyly MIM#614091
Prepair 1000+ v1.1825 WDR35 Zornitza Stark Publications for gene: WDR35 were set to
Prepair 1000+ v1.1824 WISP3 Zornitza Stark Marked gene: WISP3 as ready
Prepair 1000+ v1.1824 WISP3 Zornitza Stark Gene: wisp3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1824 WISP3 Zornitza Stark Phenotypes for gene: WISP3 were changed from Arthropathy, progressive pseudorheumatoid, of childhood, 208230 (3) to Progressive pseudorheumatoid dysplasia MIM#208230
Prepair 1000+ v1.1823 WISP3 Zornitza Stark Publications for gene: WISP3 were set to
Prepair 1000+ v1.1822 WISP3 Zornitza Stark Tag new gene name tag was added to gene: WISP3.
Prepair 1000+ v1.1822 PCDH15 Melanie Marty reviewed gene: PCDH15: Rating: GREEN; Mode of pathogenicity: None; Publications: 11398101, 11487575, 11138007, 12782354, 16260500, 14570705, 25930172, 28281779; Phenotypes: Usher syndrome, type 1F, MIM# 602083, Deafness, autosomal recessive 23, MIM# 609533; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 PCCA Melanie Marty edited their review of gene: PCCA: Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 PCCA Melanie Marty reviewed gene: PCCA: Rating: ; Mode of pathogenicity: None; Publications: 17966092, 10101253, 9887338; Phenotypes: Propionicacidemia, MIM#606054; Mode of inheritance: None
Prepair 1000+ v1.1822 OSTM1 Melanie Marty reviewed gene: OSTM1: Rating: ; Mode of pathogenicity: None; Publications: 12627228, 15108279, 16813530, 23772242, 32048120; Phenotypes: Osteopetrosis, autosomal recessive 5, MIM#259720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 500+ v1.5 OSGEP Melanie Marty reviewed gene: OSGEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828, 28272532; Phenotypes: Galloway-Mowat syndrome 3, MIM# 617729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 NEB Melanie Marty reviewed gene: NEB: Rating: GREEN; Mode of pathogenicity: None; Publications: 10051637, 22367672, 26578207, 33376055; Phenotypes: Nemaline myopathy 2, autosomal recessive 256030, Arthrogryposis multiplex congenita 6, MIM# 619334; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 TRIT1 Michelle Torres reviewed gene: TRIT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36047296, 32088416, 24901367, 28185376, 30977854; Phenotypes: Combined oxidative phosphorylation deficiency 35 MIM#617873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 WISP3 Michelle Torres reviewed gene: WISP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26610319; Phenotypes: Progressive pseudorheumatoid dysplasia MIM#208230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 WDR35 Michelle Torres reviewed gene: WDR35: Rating: GREEN; Mode of pathogenicity: None; Publications: 33421337, 29134781, 28870638, 26691894, 24027799, 21473986; Phenotypes: Cranioectodermal dysplasia 2 MIM#613610, Short-rib thoracic dysplasia 7 with or without polydactyly MIM#614091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.12 DMRT1 Jasmine Chew gene: DMRT1 was added
gene: DMRT1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: DMRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DMRT1 were set to 26139570; 38511217; 39777458
Review for gene: DMRT1 was set to GREEN
Added comment: Literature in OMIM- PMID: 26139570

New papers:
i) PMID: 38511217- heterozygous missense variant (K68N) in a Japanese man (case 13) with non-obstructive azoospermia (NOA)

ii)PMID: 39777458- heterozygous missense variant (p.Pro74Leu) in two infertile Croatian brothers with NOA in the highly conserved position within the DNA binding DM domain of the protein, and EMSA assay showed reduced DNA binding of DMRT1P74L and molecular dynamic simulations showed differences in structural and dynamical properties between the wild type protein and DMRT1P74L. Also identified additional nine infertile men with idiopathic NOA or severe oligozoospermia as carriers of missense variants (see Table 2) located in critical functional domains of DMRT1.

Note: couldn't access MONDO # as website down (phenotypes to be updated)
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 DPY19L2 Jasmine Chew gene: DPY19L2 was added
gene: DPY19L2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: DPY19L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPY19L2 were set to 15533374; 21397064; 21397064; 26516168; 30333325; 39045326
Phenotypes for gene: DPY19L2 were set to Spermatogenic failure 9, MIM# 613958
Review for gene: DPY19L2 was set to GREEN
Added comment: Literature from OMIM- PMID:15533374, 21397064, 21397064

New papers:
i) PMID: 26516168- In a cohort of Tunisian globozoospermic patients, 11 had homozygous DPY19L2 deletion, 2 had homozygous missense variant p.R298, and a patient with a novel homozygous splice site variant.

ii) PMID: 30333325- In a cohort of Chinese globozoospermic patients, 5 had DPY19L2 deletions and the other four patients carried novel DPY19L2 point variants.

iii) PMID: 39045326- homozygous variants (Arg 574Ter and Pro241Leu) in two patients with globozoospermia
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 FKBP6 Jasmine Chew gene: FKBP6 was added
gene: FKBP6 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: FKBP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKBP6 were set to 36150389
Phenotypes for gene: FKBP6 were set to Spermatogenic failure 77, MIM# 620103
Review for gene: FKBP6 was set to GREEN
Added comment: i) PMID: 36150389- compound heterozygous/ homozygous LOF variants in 6 unrelated infertile men (Dutch/German/Brazilian/Kyrgyz) with spermatogenic failure. Analysis of testicular histology was consistent with onset of germ cell loss in late meiosis and early spermiogenesis. Lack of FKBP6 expression in the testis was confirmed by RT-qPCR and immunofluorescence staining.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 GGN Jasmine Chew changed review comment from: i) PubMed: 31985809 (2020)- homozygous 1bp deletion causing a frameshift predicted to result in a premature termination codon (Gly424AlafsTer65) in 2 Turkish brothers with infertility due to globozoospermia.

ii) PubMed: 33108537 (2021)- homozygous 22bp deletion in an infertile man with globozoospermia causing a frameshift predicted to result in a premature termination codon (Leu139ArgfsTer8). The 146-amino acid mutant protein would lack the GGNBP2 (612275) and OAZ3 (605138) interaction domain, and the GGNBP1 (609495) interaction domain would be partially truncated.

iii) PMID: 23451117 (2013)- Ggn null mouse line demonstrated that s complete loss of GGN resulted in embryonic lethality at the very earliest period of pre-implantation development, with no viable blastocysts observed. This finding was consistent with the observation that Ggn mRNA was also expressed in lower levels in the oocyte and pre-implantation embryos.
Sources: Literature; to: i) PubMed: 31985809 (2020)- homozygous 1bp deletion causing a frameshift predicted to result in a premature termination codon (Gly424AlafsTer65) in 2 Turkish brothers with infertility due to globozoospermia.

ii) PubMed: 33108537 (2021)- homozygous 22bp deletion in an infertile man with globozoospermia causing a frameshift predicted to result in a premature termination codon (Leu139ArgfsTer8). The 146-amino acid mutant protein would lack the GGNBP2 (612275) and OAZ3 (605138) interaction domain, and the GGNBP1 (609495) interaction domain would be partially truncated.

iii) PMID: 23451117 (2013)- Ggn null mouse line demonstrated that s complete loss of GGN resulted in embryonic lethality at the very earliest period of pre-implantation development, with no viable blastocysts observed. This finding was consistent with the observation that Ggn mRNA was also expressed in lower levels in the oocyte and pre-implantation embryos.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 GGN Jasmine Chew changed review comment from: i) PubMed: 31985809 (2020)- hom 1bp del causing a frameshift predicted to result in a premature termination codon (Gly424AlafsTer65) in 2 Turkish brothers with infertility due to globozoospermia.

ii) PubMed: 33108537 (2021)- hom 22bp del in an infertile man with globozoospermia causing a frameshift predicted to result in a premature termination codon (Leu139ArgfsTer8). The 146-amino acid mutant protein would lack the GGNBP2 (612275) and OAZ3 (605138) interaction domain, and the GGNBP1 (609495) interaction domain would be partially truncated.

iii) PMID: 23451117 (2013)- Ggn null mouse line demonstrated that s complete loss of GGN resulted in embryonic lethality at the very earliest period of pre-implantation development, with no viable blastocysts observed. This finding was consistent with the observation that Ggn mRNA was also expressed in lower levels in the oocyte and pre-implantation embryos.
Sources: Literature; to: i) PubMed: 31985809 (2020)- homozygous 1bp deletion causing a frameshift predicted to result in a premature termination codon (Gly424AlafsTer65) in 2 Turkish brothers with infertility due to globozoospermia.

ii) PubMed: 33108537 (2021)- homozygous 22bp deletion in an infertile man with globozoospermia causing a frameshift predicted to result in a premature termination codon (Leu139ArgfsTer8). The 146-amino acid mutant protein would lack the GGNBP2 (612275) and OAZ3 (605138) interaction domain, and the GGNBP1 (609495) interaction domain would be partially truncated.

iii) PMID: 23451117 (2013)- Ggn null mouse line demonstrated that s complete loss of GGN resulted in embryonic lethality at the very earliest period of pre-implantation development, with no viable blastocysts observed. This finding was consistent with the observation that Ggn mRNA was also expressed in lower levels in the oocyte and pre-implantation embryos.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 GGN Jasmine Chew gene: GGN was added
gene: GGN was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: GGN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GGN were set to Spermatogenic failure 69, MIM# 619826
Mode of pathogenicity for gene: GGN was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: GGN was set to GREEN
Added comment: i) PubMed: 31985809 (2020)- hom 1bp del causing a frameshift predicted to result in a premature termination codon (Gly424AlafsTer65) in 2 Turkish brothers with infertility due to globozoospermia.

ii) PubMed: 33108537 (2021)- hom 22bp del in an infertile man with globozoospermia causing a frameshift predicted to result in a premature termination codon (Leu139ArgfsTer8). The 146-amino acid mutant protein would lack the GGNBP2 (612275) and OAZ3 (605138) interaction domain, and the GGNBP1 (609495) interaction domain would be partially truncated.

iii) PMID: 23451117 (2013)- Ggn null mouse line demonstrated that s complete loss of GGN resulted in embryonic lethality at the very earliest period of pre-implantation development, with no viable blastocysts observed. This finding was consistent with the observation that Ggn mRNA was also expressed in lower levels in the oocyte and pre-implantation embryos.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 NLRP5 Jasmine Chew gene: NLRP5 was added
gene: NLRP5 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: NLRP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NLRP5 were set to 30877238; 32222962; 35091966; 35946397; 33583041
Phenotypes for gene: NLRP5 were set to Oocyte/zygote/embryo maturation arrest 19, MIM# 620333
Review for gene: NLRP5 was set to GREEN
Added comment: Literature in OMIM- PMID: 30877238, 32222962, 35091966, 35946397

New evidence:
i) PMID: 33583041- homozygous missense variant (p.Asp365Asn) in an Iranian woman with 2 years of infertility, IUI-twin (HM + fetus), and two complete hydatidiform mole
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 PDHA2 Jasmine Chew changed review comment from: i) PMID: 29581481- a homozygous missense variant (M227V) in 3 infertile brothers from a consanguineous Algerian family with male infertility (owing to azoospermia, sperm immotility or necrospermia)

ii) PubMed: 35172124- previously reported homozygous missense variant (M227V) in 2 unrelated infertile Tunisian men with NOA
Sources: Literature; to: i) PMID: 29581481- a homozygous missense variant (M227V) in 3 infertile brothers from a consanguineous Algerian family with male infertility (owing to azoospermia, sperm immotility or necrospermia)

ii) PMID: 35172124- previously reported homozygous missense variant (M227V) in 2 unrelated infertile Tunisian men with NOA
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 PDHA2 Jasmine Chew gene: PDHA2 was added
gene: PDHA2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: PDHA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDHA2 were set to 29581481; 35172124
Phenotypes for gene: PDHA2 were set to Spermatogenic failure 70, MIM# 619828
Review for gene: PDHA2 was set to GREEN
Added comment: i) PMID: 29581481- a homozygous missense variant (M227V) in 3 infertile brothers from a consanguineous Algerian family with male infertility (owing to azoospermia, sperm immotility or necrospermia)

ii) PubMed: 35172124- previously reported homozygous missense variant (M227V) in 2 unrelated infertile Tunisian men with NOA
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 SYCP3 Jasmine Chew reviewed gene: SYCP3: Rating: ; Mode of pathogenicity: None; Publications: 14643120, 19110213; Phenotypes: Spermatogenic failure 4, MIM# 270960, Recurrent pregnancy loss 4, MIM# 270960; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v0.12 SYCP3 Jasmine Chew Deleted their review
Infertility and Recurrent Pregnancy Loss v0.12 SYCP3 Jasmine Chew reviewed gene: SYCP3: Rating: ; Mode of pathogenicity: None; Publications: 14643120, 19110213; Phenotypes: Spermatogenic failure 4, MIM# 270960, Recurrent pregnancy loss 4, MIM# 270960; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Infertility and Recurrent Pregnancy Loss v0.12 RXFP2 Jasmine Chew changed review comment from: i) PMID: 39222519 (2024)- a compound heterozygous variant (intragenic deletion of exon 1-5 and missense variant p.Glu77Lys) in a family with two male members affected by impaired fertility due to spermatogenic maturation arrest and a history of bilateral cryptorchidism. The Glu77Lys mutant showed no cAMP activity and hence failed to signal in response to INSL3, confirming a loss-of-function mechanism.

ii) PMID: 37208861 (2023)- Homozygous LOF (p.Phe469Serfs*8) and missense (p.Asn339Asp) variants in two unrelated infertile man with impaired spermatogenesis. The missense variant primarily impacts cell surface expression of the protein which directly correlates with reduced INSL3 activation (following protein expression studies).

iii) PMID: 38430325 - a homozygous non-canonical splicing variant (NM_130806: c.1376-12A > G) in a case with cryptorchidism and NOA, which was confirmed to cause aberrant splicing of exons 15 and 16, leading to an abnormal transcript initiation and a frameshift using minigene assay.

Note: couldn't access MONDO # as website down (phenotypes to be updated)
Sources: Literature; to: i) PMID: 39222519- a compound heterozygous variant (intragenic deletion of exon 1-5 and missense variant p.Glu77Lys) in a family with two male members affected by impaired fertility due to spermatogenic maturation arrest and a history of bilateral cryptorchidism. The Glu77Lys mutant showed no cAMP activity and hence failed to signal in response to INSL3, confirming a loss-of-function mechanism.

ii) PMID: 37208861- Homozygous LOF (p.Phe469Serfs*8) and missense (p.Asn339Asp) variants in two unrelated infertile man with impaired spermatogenesis. The missense variant primarily impacts cell surface expression of the protein which directly correlates with reduced INSL3 activation (following protein expression studies).

iii) PMID: 38430325 - a homozygous non-canonical splicing variant (NM_130806: c.1376-12A > G) in a case with cryptorchidism and NOA, which was confirmed to cause aberrant splicing of exons 15 and 16, leading to an abnormal transcript initiation and a frameshift using minigene assay.

Note: couldn't access MONDO # as website down (phenotypes to be updated)
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 RXFP2 Jasmine Chew gene: RXFP2 was added
gene: RXFP2 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: RXFP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RXFP2 were set to 39222519; 37208861; 38430325
Review for gene: RXFP2 was set to GREEN
Added comment: i) PMID: 39222519 (2024)- a compound heterozygous variant (intragenic deletion of exon 1-5 and missense variant p.Glu77Lys) in a family with two male members affected by impaired fertility due to spermatogenic maturation arrest and a history of bilateral cryptorchidism. The Glu77Lys mutant showed no cAMP activity and hence failed to signal in response to INSL3, confirming a loss-of-function mechanism.

ii) PMID: 37208861 (2023)- Homozygous LOF (p.Phe469Serfs*8) and missense (p.Asn339Asp) variants in two unrelated infertile man with impaired spermatogenesis. The missense variant primarily impacts cell surface expression of the protein which directly correlates with reduced INSL3 activation (following protein expression studies).

iii) PMID: 38430325 - a homozygous non-canonical splicing variant (NM_130806: c.1376-12A > G) in a case with cryptorchidism and NOA, which was confirmed to cause aberrant splicing of exons 15 and 16, leading to an abnormal transcript initiation and a frameshift using minigene assay.

Note: couldn't access MONDO # as website down (phenotypes to be updated)
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 SLC26A8 Jasmine Chew changed review comment from: i) PMID: 23582645- 3 heterozygous missense variants in 3 unrelated infertile men, and studies in transfected CHO-K1 cells revealed reduced interactions with CFTR and complete failure of the all three mutant to activate CFTR-dependent anion transport. Immunoblot analysis also showed that the mutant protein was significantly less abundant than wildtype and the decreased abundance of the mutant protein results from instability and proteasomal degradation.

ii) PMID: 34923715- Compound heterozygous variants in two unrelated infertile Chinese men with severe asthenozoospermia. The sperm motility of these homozygous probands was severely reduced, compared to the moderately reduced motility of sperm from the previously reported heterozygous probands (confirmed by immunoblot), consistent with SLC26A8 being the cause of their infertility phenotype,

iii) PMID: 35181959- 3 heterozygous variants ( 2-bp deletion, V731I, 1-bp deletion) in 3 unrelated infertile men with asthenoteratozoospermia, and although transfection study showed a significantly reduction of SLC26A8 expression to nearly absence in transfected HEK293 cells, immunostaining of patient sperm showed no difference in SLC26A8 expression compared to control sperm and western blot analysis of spermatozoa lysates confirmed the similar expression of SLC26A8 between patient and control sperm. Also mentioned that previous studies (PMID: 22121115 and PMID: 17517695) had shown that Slc26a8 +/- mice were fertile, whereas Slc26a8-null mice were infertile, the authors suggested that heterozygous SLC26A8 variants might not be the direct cause of the asthenoteratozoospermic phenotype observed in infertile men, and that SLC26A8-associated male infertility is likely an autosomal recessive disorder.
Sources: Literature; to: i) PMID: 23582645- 3 heterozygous missense variants in 3 unrelated infertile men, and studies in transfected CHO-K1 cells revealed reduced interactions with CFTR and complete failure of the all three mutant to activate CFTR-dependent anion transport.

ii) PMID: 34923715- Compound heterozygous variants in two unrelated infertile Chinese men with severe asthenozoospermia. The sperm motility of these homozygous probands was severely reduced, compared to the moderately reduced motility of sperm from the previously reported heterozygous probands (confirmed by immunoblot), consistent with SLC26A8 being the cause of their infertility phenotype,

iii) PMID: 35181959- 3 heterozygous variants ( 2-bp deletion, V731I, 1-bp deletion) in 3 unrelated infertile men with asthenoteratozoospermia. Although transfection study showed a significantly reduction of SLC26A8 expression to nearly absence in transfected HEK293 cells, immunostaining of patient sperm showed no difference in SLC26A8 expression compared to control sperm and western blot analysis of spermatozoa lysates confirmed the similar expression of SLC26A8 between patient and control sperm. Also mentioned that previous studies (PMID: 22121115 and PMID: 17517695) had shown that Slc26a8 +/- mice were fertile, whereas Slc26a8-null mice were infertile, the authors suggested that heterozygous SLC26A8 variants might not be the direct cause of the asthenoteratozoospermic phenotype observed in infertile men, and that SLC26A8-associated male infertility is likely an autosomal recessive disorder.
Infertility and Recurrent Pregnancy Loss v0.12 SLC26A8 Jasmine Chew gene: SLC26A8 was added
gene: SLC26A8 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: SLC26A8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SLC26A8 were set to 23582645; 34923715; 35181959
Phenotypes for gene: SLC26A8 were set to Spermatogenic failure 3, MIM# 606766
Review for gene: SLC26A8 was set to GREEN
Added comment: i) PMID: 23582645- 3 heterozygous missense variants in 3 unrelated infertile men, and studies in transfected CHO-K1 cells revealed reduced interactions with CFTR and complete failure of the all three mutant to activate CFTR-dependent anion transport. Immunoblot analysis also showed that the mutant protein was significantly less abundant than wildtype and the decreased abundance of the mutant protein results from instability and proteasomal degradation.

ii) PMID: 34923715- Compound heterozygous variants in two unrelated infertile Chinese men with severe asthenozoospermia. The sperm motility of these homozygous probands was severely reduced, compared to the moderately reduced motility of sperm from the previously reported heterozygous probands (confirmed by immunoblot), consistent with SLC26A8 being the cause of their infertility phenotype,

iii) PMID: 35181959- 3 heterozygous variants ( 2-bp deletion, V731I, 1-bp deletion) in 3 unrelated infertile men with asthenoteratozoospermia, and although transfection study showed a significantly reduction of SLC26A8 expression to nearly absence in transfected HEK293 cells, immunostaining of patient sperm showed no difference in SLC26A8 expression compared to control sperm and western blot analysis of spermatozoa lysates confirmed the similar expression of SLC26A8 between patient and control sperm. Also mentioned that previous studies (PMID: 22121115 and PMID: 17517695) had shown that Slc26a8 +/- mice were fertile, whereas Slc26a8-null mice were infertile, the authors suggested that heterozygous SLC26A8 variants might not be the direct cause of the asthenoteratozoospermic phenotype observed in infertile men, and that SLC26A8-associated male infertility is likely an autosomal recessive disorder.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 SYCP3 Jasmine Chew Deleted their review
Infertility and Recurrent Pregnancy Loss v0.12 SYCP3 Jasmine Chew gene: SYCP3 was added
gene: SYCP3 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: SYCP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYCP3 were set to 14643120; 19110213
Phenotypes for gene: SYCP3 were set to Spermatogenic failure 4, Recurrent pregnancy loss 4, MIM# 270960
Review for gene: SYCP3 was set to GREEN
Added comment: Spermatogenic failure 4, MIM# 270960
i) PMID: 14643120- identified a heterozygous 1-bp deletion (643delA) in 2 unrelated patients with azoospermia with with maturation arrest , resulting in a premature stop codon and truncation of the C-terminal, coiled-coil-forming region of the protein. The mutant protein showed greatly reduced interaction with the wildtype protein in vitro and interfered with SYCP3 fiber formation in cultured cells. The results suggested that SYCP3 has an essential meiotic function in human spermatogenesis that is compromised by the mutant protein by dominant-negative interference.

Pregnancy loss, recurrent, 4, MIM# 270960
i) PMID: 19110213- identified a heterozygous deletion and a point variant (-16delACTT in intron 7 and 657T-C transition at the last nucleotide of exon 8) in 2 of the women with recurrent pregnancy loss that were not found in 150 fertile women. Both mutant proteins were shown to inhibit normal fiber formation of SYCP3 when coexpressed in a heterologous system. This suggested that the heterozygous variants are likely to form aberrant lateral elements in the synaptonemal complex in a dominant-negative manner, possibly leading to abnormal chromosomal behavior in meiosis I during oogenesis that might lead to recurrent miscarriage. Also noted that the SYCP3-related phenotype in humans, in which affected males are infertile whereas affected females have recurrent pregnancy loss, is similar to that seen in Sycp3-deficient mice (Yuan et al., 2000; Yuan et al., 2002).
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 KHDC3L Jasmine Chew gene: KHDC3L was added
gene: KHDC3L was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: KHDC3L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KHDC3L were set to 21885028; 19246479; 23232697; 31847873; 31609975; 29606347
Phenotypes for gene: KHDC3L were set to Recurrent hydatidiform mole 2, MIM# 614293
Added comment: Biallelic variants have been reported for several unrelated families with recurrent complete hydatidiform mole (CHM) pregnancy- predominantly biparental and RPL- PMID: 21885028, 19246479, 23232697.

New evidence-
i) PMID 31847873: homozygous LOF variant in a woman with multiple consanguineous marriages in her extended family and history of 2 biparental complete hydatidiform mole (BiCHM) and methylation study on her oocytes revealed a genome-wide deficit of DNA methylation compared with normal human oocytes.

ii) PMID: 31609975- two deletions of KHDC3L (p.E150_V160del and p.E150_V172del) in female RPL patients, both of which harbor a common loss of Thr156 and are impaired in PARP1 activation and homologous recombination (HR) repair. Also provided functional evidence that KHDC3L dysfunction causes PARP1 inhibition and HR-mediated DNA repair deficiency, which is synthetically lethal.

iii) PMID: 29606347- a novel homozygous frameshift p.Q15Rfs*25 variant in a female patient (II-1) from family 4 with a history of 2 spontaneous abortions and x2 partial hydatidiform moles, and her embryos formed after ICSI are fertilized normally but arrest at the morula stage.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 PADI6 Jasmine Chew gene: PADI6 was added
gene: PADI6 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: PADI6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PADI6 were set to 29693651; 33583041; 33221824; 27730629; 27545678
Phenotypes for gene: PADI6 were set to Oocyte/zygote/embryo maturation arrest 16, #MIM 617234
Review for gene: PADI6 was set to GREEN
Added comment: i) PMID: 29693651- a compound het variant (N598S and R682Q) in a female with a total of six pregnancy losses from natural spontaneous conceptions, two of them were initially diagnosed as miscarriages and four as molar pregnancy.

ii) PMID: 33583041- a novel homozygous missense variant (p.Ile599Asn) in a woman with a total of seven pregnancy losses from spontaneous conceptions, four HMs including two with fetuses and three miscarriages.

iii) PMID: 33221824- a compound het variant (p.Thr372Ala and p.Trp690*) in a German woman with and miscarriages and also occurrence of multilocus imprinting disturbance (MLID) in two children each carrying a heterozygous variant..

iv) PMID: 27730629- a homozygous nonsense variant (p.Arg457*) in a Saudi woman with primary infertility and early development arrest during embryonic cleavage stages after in vitro fertilization.

v) PMID: 27545678- homozygous nonsense variant (p.Gln381∗) in one familial case (consisting of three sisters) and compound heterozygous variants in 2 other unrelated patients with primary infertility and early development arrest during embryonic cleavage stages after in vitro fertilization.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 CCNB3 Jasmine Chew changed review comment from: i) PMID: 35722368- homozygous missense variant (p.P119Q) in the female of unexplained recurrent pregnancy loss (RPL) couple (couple 29)
ii) PMID: 32938693- homozygous missense variant (p.V1251D) in two sisters with RPL and two of their POCs were characterised and found to be triploid digynic due to the failure of meiosis II.
iii) PMID: 34021051- novel homozygous frameshift variant (p.Val1321Glyfs*4, due to splicing causing exon skipping) in a patient with 16 RPL and one of her miscarriages is triploid digynic resulted from the failure of meiosis I.

Supporting mouse evidence:
iv) PMID: 30770433- Ccnb3 knockout also causes female infertility due to the failure of metaphase to anaphase transition in meiosis I and the extrusion of the first polar body. The infertility in these mice appeared to be due to embryonic lethality before embryonic day 7.5 and some of their oocytes fertilised by intracytoplasmic sperm injection led to triploid embryos.
v) PMID: 34850816- Ccnb3-deficient mouse model is similar to a human infertility condition—recurrent pregnancy loss (RPL). Their findings demonstrate that the triploidy of embryos derived from Ccnb3-deficient oocytes is the primary cause of embryo death (i.e., such embryos can be rescued with euploid nuclei, whereas cytoplasmic Ccnb3 transcript is dispensable for zygotic genome activation and embryo development).

Note: couldn't access MONDO # as website down (phenotypes to be updated)
Sources: Literature
Sources: Literature; to: i) PMID: 35722368- homozygous missense variant (p.P119Q) in the female of unexplained recurrent pregnancy loss (RPL) couple (couple 29)
ii) PMID: 32938693- homozygous missense variant (p.V1251D) in two sisters with RPL and two of their POCs were characterised and found to be triploid digynic due to the failure of meiosis II.
iii) PMID: 34021051- novel homozygous frameshift variant (p.Val1321Glyfs*4, due to splicing causing exon skipping) in a patient with 16 RPL and one of her miscarriages is triploid digynic resulted from the failure of meiosis I.

Supporting mouse evidence:
iv) PMID: 30770433- Ccnb3 knockout also causes female infertility due to the failure of metaphase to anaphase transition in meiosis I and the extrusion of the first polar body. The infertility in these mice appeared to be due to embryonic lethality before embryonic day 7.5 and some of their oocytes fertilised by intracytoplasmic sperm injection led to triploid embryos.
v) PMID: 34850816- Ccnb3-deficient mouse model is similar to a human infertility condition—recurrent pregnancy loss (RPL). Their findings demonstrate that the triploidy of embryos derived from Ccnb3-deficient oocytes is the primary cause of embryo death (i.e., such embryos can be rescued with euploid nuclei, whereas cytoplasmic Ccnb3 transcript is dispensable for zygotic genome activation and embryo development).

Note: couldn't access MONDO # as website down (phenotypes to be updated)
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 CCNB3 Jasmine Chew edited their review of gene: CCNB3: Changed rating: GREEN
Infertility and Recurrent Pregnancy Loss v0.12 CCNB3 Jasmine Chew gene: CCNB3 was added
gene: CCNB3 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: CCNB3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCNB3 were set to 35722368; 32938693; 34021051; 30770433; 34850816
Added comment: i) PMID: 35722368- homozygous missense variant (p.P119Q) in the female of unexplained recurrent pregnancy loss (RPL) couple (couple 29)
ii) PMID: 32938693- homozygous missense variant (p.V1251D) in two sisters with RPL and two of their POCs were characterised and found to be triploid digynic due to the failure of meiosis II.
iii) PMID: 34021051- novel homozygous frameshift variant (p.Val1321Glyfs*4, due to splicing causing exon skipping) in a patient with 16 RPL and one of her miscarriages is triploid digynic resulted from the failure of meiosis I.

Supporting mouse evidence:
iv) PMID: 30770433- Ccnb3 knockout also causes female infertility due to the failure of metaphase to anaphase transition in meiosis I and the extrusion of the first polar body. The infertility in these mice appeared to be due to embryonic lethality before embryonic day 7.5 and some of their oocytes fertilised by intracytoplasmic sperm injection led to triploid embryos.
v) PMID: 34850816- Ccnb3-deficient mouse model is similar to a human infertility condition—recurrent pregnancy loss (RPL). Their findings demonstrate that the triploidy of embryos derived from Ccnb3-deficient oocytes is the primary cause of embryo death (i.e., such embryos can be rescued with euploid nuclei, whereas cytoplasmic Ccnb3 transcript is dispensable for zygotic genome activation and embryo development).

Note: couldn't access MONDO # as website down (phenotypes to be updated)
Sources: Literature
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 CDC20 Jasmine Chew gene: CDC20 was added
gene: CDC20 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: CDC20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDC20 were set to 32666501; 33683667; 33898437; 34218387
Phenotypes for gene: CDC20 were set to Oocyte/zygote/embryo maturation arrest 14, MIM# 620276
Review for gene: CDC20 was set to GREEN
Added comment: i) PMID: 32666501- Biallelic (homozygous/compound heterozygous) variants in 5 unrelated Chinese women with infertility due to oocyte maturation arrest. Knocked down mouse oocytes showed an metaphase I (MI) arrest phenotype that could be rescued by injection of wildtype human CDC20 cRNA; all of the variants significantly reduced the ability of CDC20 to rescue the phenotype.

ii) PMID: 33683667- a compound heterozygous (missense and nonsense) variant in a Chinese woman with infertility due to oocyte maturation abnormalities and early embryonic arrest.

iii) PMID: 33898437- 4 patients from 3 Chinese families with homozygous or compound heterozygous variants with infertility due to oocyte maturation arrest, fertilization failure, and early embryonic arrest. Functional analysis in mouse oocytes with knockdown of Cdc20 showed that the homozygous and compound heterozygous variants significantly reduced the ability of CDC20 to rescue the lack of PB1 extrusion (MI arrest).

iv) PMID: 34218387- homozygous missense variant in a Chinese woman with infertility due to oocyte maturation arrest at MI and fertilization failure of MII oocytes.
Sources: Literature
Prepair 1000+ v1.1822 NDP Melanie Marty reviewed gene: NDP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23444378, 8268931, 17325173, 27217716, 29181528, 31827910; Phenotypes: Norrie disease, MIM# 310600; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.1822 NCF2 Melanie Marty reviewed gene: NCF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27178966, 7795241, 10498624; Phenotypes: Chronic granulomatous disease 2, autosomal recessive, MIM# 233710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 MYD88 Melanie Marty reviewed gene: MYD88: Rating: GREEN; Mode of pathogenicity: None; Publications: 18669862, 20538326, 31301515; Phenotypes: Immunodeficiency 68, MIM# 612260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 MSTO1 Melanie Marty reviewed gene: MSTO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28554942, 28544275, 31604776, 31463572, 31130378, 30684668, 29339779; Phenotypes: Myopathy, mitochondrial, and ataxia, MIM# 617675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 MICU1 Melanie Marty reviewed gene: MICU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24336167, 29721912, 32395406; Phenotypes: Myopathy with extrapyramidal signs, MIM# 615673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.12 TACC3 Jasmine Chew changed review comment from: PMID: 36395215- compound heterozygous variants (Patient 1- p.Ser177Thr/p.Pro395Arg, Patient 2- p.Lys225_Cys236del/p.Gly631Val) in two unrelated females presented with oocyte maturation arrest and undetectable spindles on both polarization and fluorescence microscopy. Their oocytes lacked huoMTOCs and had poorly organized microtubules, similar to the phenotype of TACC3 depletion in vitro, which suggests a loss-of-function mechanism causing oocyte maturation arrest and infertility.
Sources: Literature; to: PMID: 36395215- compound heterozygous variants (Patient 1- p.Ser177Thr/p.Pro395Arg, Patient 2- p.Lys225_Cys236del/p.Gly631Val) in two unrelated females presented with oocyte maturation arrest and undetectable spindles on both polarization and fluorescence microscopy. Their oocytes lacked huoMTOCs and had poorly organized microtubules, similar to the phenotype of TACC3 depletion in vitro, which suggests a loss-of-function mechanism causing oocyte maturation arrest and infertility.

Note: couldn't access MONDO # as website down (phenotypes to be updated)
Infertility and Recurrent Pregnancy Loss v0.12 TACC3 Jasmine Chew gene: TACC3 was added
gene: TACC3 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: TACC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TACC3 were set to 36395215
Review for gene: TACC3 was set to GREEN
Added comment: PMID: 36395215- compound heterozygous variants (Patient 1- p.Ser177Thr/p.Pro395Arg, Patient 2- p.Lys225_Cys236del/p.Gly631Val) in two unrelated females presented with oocyte maturation arrest and undetectable spindles on both polarization and fluorescence microscopy. Their oocytes lacked huoMTOCs and had poorly organized microtubules, similar to the phenotype of TACC3 depletion in vitro, which suggests a loss-of-function mechanism causing oocyte maturation arrest and infertility.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.12 ELL3 Jasmine Chew gene: ELL3 was added
gene: ELL3 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: ELL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ELL3 were set to 39820605
Review for gene: ELL3 was set to GREEN
Added comment: PMID:39820605- 8 different heterozygous variants (5 missense, 3 splicing) in 8 unrelated couples who experienced consecutive early miscarriages due to embryonic aneuploidy. For the three splice variants, mini-gene splicing assays revealed that all led to abnormal splicing, and consequently premature termination of translation or exon skipping, consistent with LOF effect. Findings from functional analysis on human oocytes and knockout mouse oocytes overall supporting that ELL3 depletion increases the incidence of meiotic spindle abnormality and oocyte aneuploidy.
Note: couldn't access MONDO # as website down (phenotypes to be updated)
Sources: Literature
Prepair 1000+ v1.1822 VIPAS39 Michelle Torres reviewed gene: VIPAS39: Rating: GREEN; Mode of pathogenicity: None; Publications: 20190753, 35151346; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2 MIM#613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 TRMT10A Michelle Torres reviewed gene: TRMT10A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24204302, 25053765, 33448213, 33067246, 26535115, 26526202, 26297882; Phenotypes: Microcephaly, short stature, and impaired glucose metabolism 1 MIM#616033; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 TRAPPC12 Michelle Torres reviewed gene: TRAPPC12: Rating: GREEN; Mode of pathogenicity: None; Publications: 32369837, 28777934; Phenotypes: Encephalopathy, progressive, early-onset, with brain atrophy and spasticity MIM#617669; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 SCNN1B Crystle Lee reviewed gene: SCNN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 26807262; Phenotypes: Pseudohypoaldosteronism, type IB2, autosomal recessive, MIM#620125; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 TRAPPC11 Michelle Torres reviewed gene: TRAPPC11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23830518, 26322222, 29855340, 30105108, 38564972; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 18 MIM#615356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 SLC30A10 Crystle Lee reviewed gene: SLC30A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 38283630, 34877518, 22341971; Phenotypes: Hypermanganesemia with dystonia 1, MIM#613280; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 SLC7A7 Crystle Lee reviewed gene: SLC7A7: Rating: GREEN; Mode of pathogenicity: None; Publications: 17764084; Phenotypes: Lysinuric protein intolerance, MIM#222700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 STIM1 Crystle Lee reviewed gene: STIM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31448844, 20876309, 25935105; Phenotypes: Immunodeficiency 10, MIM#612783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 LRSAM1 Melanie Marty reviewed gene: LRSAM1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 38330802, 33568173; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2P, MIM# 614436; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 TPP1 Michelle Torres reviewed gene: TPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31283065; Phenotypes: Ceroid lipofuscinosis, neuronal, 2 MIM#204500, Spinocerebellar ataxia, autosomal recessive 7 MIM#609270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 TOE1 Michelle Torres reviewed gene: TOE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28092684, 36738896; Phenotypes: Pontocerebellar hypoplasia, type 7 MIM#614969; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 LONP1 Melanie Marty reviewed gene: LONP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31636596; Phenotypes: CODAS syndrome, MIM#600373; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 TBC1D20 Michelle Torres reviewed gene: TBC1D20: Rating: GREEN; Mode of pathogenicity: None; Publications: 24239381, 32740904, 32162791; Phenotypes: Warburg micro syndrome 4 MIM#615663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.12 WNT6 Jasmine Chew gene: WNT6 was added
gene: WNT6 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: WNT6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WNT6 were set to 36385415; 25750203
Phenotypes for gene: WNT6 were set to recurrent pregnancy loss susceptibility, MONDO:0000144
Review for gene: WNT6 was set to GREEN
Added comment: i) PMID: 36385415- heterozygous missense variant (p.Arg70Gly) in a female with recurrent pregnancy loss (C21)

ii) PMID: 25750203- four novel heterozygous (checked Sanger traces) variants (i.e, one missense P.Leu148Arg, one synonymous c. 522C>T, one variant in intron 1 c. 297+40G>A, and one variant in the 3′UTR c. 1127G>A ) in 4 women with unexplained recurrent miscarriages (RM), but only the missense variant was shown to affect the functional region of WNT6 that might explain the unexplained RM
Sources: Literature
Prepair 1000+ v1.1822 XYLT2 Michelle Torres reviewed gene: XYLT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34925453, 26027496, 26987875, 30891060, 28484880; Phenotypes: Spondyloocular syndrome MIM#605822; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 CLN3 Lilian Downie Marked gene: CLN3 as ready
Prepair 1000+ v1.1822 CLN3 Lilian Downie Added comment: Comment when marking as ready: Consider exclusion (Amber) as we will miss a high proportion of cases due to the founder variant being a 1kb deletion
Prepair 1000+ v1.1822 CLN3 Lilian Downie Gene: cln3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1822 CLN3 Lilian Downie Tag for review tag was added to gene: CLN3.
Prepair 1000+ v1.1822 XRCC4 Michelle Torres reviewed gene: XRCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24389050, 25728776, 25872942; Phenotypes: Short stature, microcephaly, and endocrine dysfunction MIM#616541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 MLC1 Kate Scarff reviewed gene: MLC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11254442, 18757878, 20301707, 29661901; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts 1, MIM #604004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.12 USP26 Jasmine Chew gene: USP26 was added
gene: USP26 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: USP26 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: USP26 were set to 34202084; 27089915
Phenotypes for gene: USP26 were set to Spermatogenic failure, X-linked 6, MIM# 301101
Review for gene: USP26 was set to GREEN
Added comment: i) PMID: 34202084- hemizygous missense variants in 2 unrelated affected Chinese men with infertility due to asthenoteratozoospermia (R825G in proband H002, and N799S in proband H042) and functional analysis showed markedly reduced USP26 mRNA and protein levels in patient sperm.

ii) PMID: 27089915- a novel hemizygous missense variant R344W in two affected Chinese men with non-obstructive azoospermia, which has been shown functionally to have reduce binding affinity and deubiquitinating activity of USP26 to androgen receptors.
Sources: Literature
Prepair 1000+ v1.1822 USH1G Michelle Torres reviewed gene: USH1G: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301442; Phenotypes: Usher syndrome, type 1G MIM#606943; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 METTL23 Kate Scarff reviewed gene: METTL23: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24501276, 24626631, 39152716, 32878022, 32439618, 32067349; Phenotypes: Intellectual developmental disorder, autosomal recessive 44, MIM #615942; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 UBE3B Michelle Torres reviewed gene: UBE3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 23200864, 23200864, 34012380, 32949109, 27763745; Phenotypes: Kaufman oculocerebrofacial syndrome MIM#244450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2429 CDKL1 Sarah Milton gene: CDKL1 was added
gene: CDKL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDKL1 were set to PMID: 40088891
Phenotypes for gene: CDKL1 were set to Neurodevelopmental disorder, MONDO:0700092, CDKL1-related
Mode of pathogenicity for gene: CDKL1 was set to Other
Review for gene: CDKL1 was set to AMBER
Added comment: CDKL1 encodes a cyclin dependent kinase of which there are CDKL1-5 in humans.
(CDKL5 has been associated with a neurodevelopmental disorder previously.)

Bereshneh et al describe 2 individuals with a neurodevelopmental disorder with de novo variants in CDKL1 sourced from databases containing individuals with neurodevelopmental disorders, no additional phenotypic information was provided. Both variants were missense and present in the population (c.505C>T - 13 heterozygotes in gnomad 4, c.344T>C - 2 heterozygotes gnomad 4).

Both missense variants were located in the kinase domain and dominant negative mechanism was postulated based on drosophilia studies.

Functional studies in drosphilia showed variants seen in probands partially rescued a loss of function model however overexpression of transcripts containing the variants resulted in a more severe phenotype suggesting dominant negative.
Authors also noted the larger than expected number of LOF variants in gnomad for the disease to be caused by this mechanism.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.96 CDKL1 Sarah Milton gene: CDKL1 was added
gene: CDKL1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CDKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDKL1 were set to PMID: 40088891
Phenotypes for gene: CDKL1 were set to Neurodevelopmental disorder, MONDO:0700092, CDKL1-related
Mode of pathogenicity for gene: CDKL1 was set to Other
Review for gene: CDKL1 was set to AMBER
Added comment: CDKL1 encodes a cyclin dependent kinase of which there are CDKL1-5 in humans.
(CDKL5 has been associated with a neurodevelopmental disorder previously.)

Bereshneh et al describe 2 individuals with a neurodevelopmental disorder with de novo variants in CDKL1 sourced from databases containing individuals with neurodevelopmental disorders, no additional phenotypic information was provided. Both variants were missense and present in the population (c.505C>T - 13 heterozygotes in gnomad 4, c.344T>C - 2 heterozygotes gnomad 4).

Both missense variants were located in the kinase domain and dominant negative mechanism was postulated based on drosophilia studies.

Functional studies in drosphilia showed variants seen in probands partially rescued a loss of function model however overexpression of transcripts containing the variants resulted in a more severe phenotype suggesting dominant negative.
Authors also noted the larger than expected number of LOF variants in gnomad for the disease to be caused by this mechanism.
Sources: Literature
Mendeliome v1.2429 CDKL2 Sarah Milton gene: CDKL2 was added
gene: CDKL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDKL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDKL2 were set to PMID: 40088891
Phenotypes for gene: CDKL2 were set to Neurodevelopmental disorder, MONDO:0700092, CDKL2-related
Mode of pathogenicity for gene: CDKL2 was set to Other
Review for gene: CDKL2 was set to AMBER
Added comment: CDKL2 encodes a cyclin dependent kinase of which there are CDKL1-5 in humans.
(CDKL5 has been associated with a neurodevelopmental disorder previously.)

Bereshneh et al describe 5 individuals with a neurodevelopmental disorder with de novo variants in CDKL2. 3 variants were missense, 1 was an in frame single amino acid deletion.
2 of the individuals described were monozygotic twins who were born at 30/40 and also had PVL on neuroimaging.

Phenotype included GDD (5/5) - severity not described, speech impairment (5/5), motor impairment (4/5), epilepsy (3/5), ID (3/5), IUGR (3/5), poor growth postnatally (3/5), GI/feeding issues (3/5), tone abnormality (3/5)

Missense variants were located in the kinase domain and dominant negative mechanism was postulated based on drosophilia studies.

Functional studies in drosphilia showed variants seen in probands did not completely rescue a loss of function model, as well as this, overexpression of transcripts containing the variants resulted in a more severe phenotype suggesting dominant negative.
Authors also noted the larger than expected number of LOF variants in gnomad for the disease to be caused by this mechanism.
Sources: Literature
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.96 CDKL2 Sarah Milton gene: CDKL2 was added
gene: CDKL2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CDKL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDKL2 were set to PMID: 40088891
Phenotypes for gene: CDKL2 were set to Neurodevelopmental disorder, MONDO:0700092, CDKL2-related
Penetrance for gene: CDKL2 were set to Complete
Mode of pathogenicity for gene: CDKL2 was set to Other
Review for gene: CDKL2 was set to AMBER
Added comment: CDKL2 encodes a cyclin dependent kinase of which there are CDKL1-5 in humans.
(CDKL5 has been associated with a neurodevelopmental disorder previously.)

Bereshneh et al describe 5 individuals with a neurodevelopmental disorder with de novo variants in CDKL2. 3 variants were missense, 1 was an in frame single amino acid deletion.
2 of the individuals described were monozygotic twins who were born at 30/40 and also had PVL on neuroimaging.

Phenotype included GDD (5/5) - severity not described, speech impairment (5/5), motor impairment (4/5), epilepsy (3/5), ID (3/5), IUGR (3/5), poor growth postnatally (3/5), GI/feeding issues (3/5), tone abnormality (3/5)

Missense variants were located in the kinase domain and dominant negative mechanism was postulated based on drosophilia studies.

Functional studies in drosphilia showed variants seen in probands did not completely rescue a loss of function model, as well as this, overexpression of transcripts containing the variants resulted in a more severe phenotype suggesting dominant negative.
Authors also noted the larger than expected number of LOF variants in gnomad for the disease to be caused by this mechanism.
Sources: Literature
Prepair 1000+ v1.1822 MEGF10 Kate Scarff reviewed gene: MEGF10: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22101682, 22371254, 39654599, 36349186, 35370044, 34828389; Phenotypes: Congenital myopathy 10A, severe variant, MIM #614399, Congenital myopathy 10B, mild variant, MIM #620249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1822 LRAT Kate Scarff reviewed gene: LRAT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11381255, 18055821, 22570351, 29973277, 24625443, 31448181; Phenotypes: Retinal dystrophy, early-onset severe, Leber congenital amaurosis 14, Retinitis pigmentosa, juvenile, all under MIM #613341; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2429 TEX11 Zornitza Stark Marked gene: TEX11 as ready
Mendeliome v1.2429 TEX11 Zornitza Stark Gene: tex11 has been classified as Green List (High Evidence).
Mendeliome v1.2429 TEX11 Zornitza Stark Classified gene: TEX11 as Green List (high evidence)
Mendeliome v1.2429 TEX11 Zornitza Stark Gene: tex11 has been classified as Green List (High Evidence).
Mendeliome v1.2428 TEX11 Zornitza Stark gene: TEX11 was added
gene: TEX11 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TEX11 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TEX11 were set to 25970010; 29661171; 34621296; 37124723
Phenotypes for gene: TEX11 were set to Spermatogenic failure, X-linked 2, MIM# 309120
Review for gene: TEX11 was set to GREEN
Added comment: i) PMID:25970010- hemizygous variants in 7 out of of 289 azoospermic men, including a 90kb exonic deletion (Ex10-12) in 2 European men, 2 missense variants in 2 European/German men, and 3 splice variants in two white and one Arabic men.
ii) PMID: 29661171 (2018)- a novel hemizygous missense variant (W856C) in two brothers with azoospermia (absent in the mother- ?can it be gonadal mosaicism). Their testicular biopsy revealed meiotic arrest and no post-meiotic round spermatids and mature spermatozoa were observed.
iii) PMID: 34621296 (2021)- seven novel hemizygous variants in three familial (one missense, two splice) and four NOA-affected sporadic (three frameshift, one nonsense) cases iv) PMID: 37124723 (2023)- three novel hemizygous variants ( p.R105*, p.K143Q, and p.G859R) in three unrelated NOA males and their histological analysis of testicular biopsy specimens revealed thicker basement membrane of the seminiferous tubules and poorly developed spermatocytes.
Sources: Expert Review
Infertility and Recurrent Pregnancy Loss v0.12 TEX11 Zornitza Stark Marked gene: TEX11 as ready
Infertility and Recurrent Pregnancy Loss v0.12 TEX11 Zornitza Stark Gene: tex11 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.12 TEX11 Zornitza Stark Phenotypes for gene: TEX11 were changed from #MIM:309120 to Spermatogenic failure, X-linked 2, MIM# 309120
Infertility and Recurrent Pregnancy Loss v0.11 TEX11 Zornitza Stark Classified gene: TEX11 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.11 TEX11 Zornitza Stark Gene: tex11 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.10 TEX11 Zornitza Stark reviewed gene: TEX11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure, X-linked 2, MIM# 309120; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.2427 SPAG6 Zornitza Stark Marked gene: SPAG6 as ready
Mendeliome v1.2427 SPAG6 Zornitza Stark Gene: spag6 has been classified as Green List (High Evidence).
Mendeliome v1.2427 SPAG6 Zornitza Stark Classified gene: SPAG6 as Green List (high evidence)
Mendeliome v1.2427 SPAG6 Zornitza Stark Gene: spag6 has been classified as Green List (High Evidence).
Mendeliome v1.2426 SPAG6 Zornitza Stark gene: SPAG6 was added
gene: SPAG6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPAG6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPAG6 were set to 35232447; 38073178; 32124190
Phenotypes for gene: SPAG6 were set to Spermatogenic failure, MONDO:0004983, SPAG6-related
Review for gene: SPAG6 was set to GREEN
Added comment: i) PMID: 35232447- two homozygous variants (F1 II-1: p. A103D; F2 II-1:p. K196Sfs*6) in two unrelated Han Chinese men with nonsyndromic asthenoteratozoospermia with severe multiple morphological abnormalities of the sperm flagella. Immunostaining and WB showed lower SPAG6 expression in spermatozoa of both affected males. The couple with the missense variant as able to conceive successfully after undergoing ICSI.
ii) PMID: 38073178- a homozygous missense p.R310W in three brothers (two brothers with both asthenozoospermia and oligozoospermia, third brother with azoospermia)
iii) PMID: 32124190- a novel compound heterozygous variant (c.143_145del: p.48_49del, c.585delA: p.Lys196Serfs*6) in an infertile PCD patient with severe with asthenoteratozoospermia, presented with morphological defects of sperm flagella and lower mRNA and protein expression in mutant sperm.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.10 SPAG6 Zornitza Stark Marked gene: SPAG6 as ready
Infertility and Recurrent Pregnancy Loss v0.10 SPAG6 Zornitza Stark Gene: spag6 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.10 SPAG6 Zornitza Stark Phenotypes for gene: SPAG6 were changed from MONDO:0004983 to Spermatogenic failure, MONDO:0004983, SPAG6-related
Infertility and Recurrent Pregnancy Loss v0.9 SPAG6 Zornitza Stark Classified gene: SPAG6 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.9 SPAG6 Zornitza Stark Gene: spag6 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.8 SPAG6 Zornitza Stark reviewed gene: SPAG6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure, MONDO:0004983, SPAG6-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2425 SEPT12 Zornitza Stark Marked gene: SEPT12 as ready
Mendeliome v1.2425 SEPT12 Zornitza Stark Gene: sept12 has been classified as Green List (High Evidence).
Mendeliome v1.2425 SEPT12 Zornitza Stark Classified gene: SEPT12 as Green List (high evidence)
Mendeliome v1.2425 SEPT12 Zornitza Stark Gene: sept12 has been classified as Green List (High Evidence).
Mendeliome v1.2424 SEPT12 Zornitza Stark gene: SEPT12 was added
gene: SEPT12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEPT12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SEPT12 were set to 22479503; 22275165; 35547809
Phenotypes for gene: SEPT12 were set to Spermatogenic failure 10, MIM#614822
Review for gene: SEPT12 was set to GREEN
Added comment: i) PMID: 22479503- A homozygous truncating variant (c.474 G>A) in 15 unrelated infertile men and 9 of them had teratozoospermia (88 to 99% of abnormal sperm);Transfection studies also showed that the mutant SEPT12 disrupted filament formation of wildtype SEPT12 in a dose-dependent manner.
ii) PMID:22275165- Two heterozygous missense variants (T89M and D197N) in a man with asthenoteratozoospermia and another man with oligoasthenozoospermia. Functional analysis demonstrated that both mutations adversely affected filament formation of wildtype SEPT12 in a dose-dependent manner.
iii) PMID: 35547809- A heterozygous missense variant (p.Cys24Ter) in the male partner of a patient couple, who had a previous fertilization failure (FF) after intracytoplasmic sperm injection (ICSI) and became pregnant after ICSI together with artificial oocyte activation (AOA). Their Septin12 knockout mice study also showed that Septin12 -/- male mice are infertile with reduced sperm counts and abnormal sperm morphology but male Septin12 +/− mice are fertile. This observation contradicted with the previous studies showed that male Septin12 +/− chimeric mice are infertile (Lin et al., 2009, PMID: 19359518). The main difference is that the Septin12 +/− chimeric mice were generated in Lin et al., 2009 (PMID: 19359518) was by blastocyst injection of Septin12 +/− embryonic stem cells (ESCs), while their Septin12 +/− founder mice were established by CRISPR/Cas9 mediated gene editing in the zygote. The quality of injected Septin12 +/− ESCs might affect the experimental result.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.8 SEPT12 Zornitza Stark Marked gene: SEPT12 as ready
Infertility and Recurrent Pregnancy Loss v0.8 SEPT12 Zornitza Stark Gene: sept12 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.8 SEPT12 Zornitza Stark Phenotypes for gene: SEPT12 were changed from #MIM:614822 to Spermatogenic failure 10, MIM#614822
Infertility and Recurrent Pregnancy Loss v0.7 SEPT12 Zornitza Stark Classified gene: SEPT12 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.7 SEPT12 Zornitza Stark Gene: sept12 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.6 SEPT12 Zornitza Stark reviewed gene: SEPT12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 10, MIM#614822; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2423 PLCZ1 Zornitza Stark Marked gene: PLCZ1 as ready
Mendeliome v1.2423 PLCZ1 Zornitza Stark Gene: plcz1 has been classified as Green List (High Evidence).
Mendeliome v1.2423 PLCZ1 Zornitza Stark Classified gene: PLCZ1 as Green List (high evidence)
Mendeliome v1.2423 PLCZ1 Zornitza Stark Gene: plcz1 has been classified as Green List (High Evidence).
Mendeliome v1.2422 PLCZ1 Zornitza Stark gene: PLCZ1 was added
gene: PLCZ1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLCZ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLCZ1 were set to 26721930; 31463947; 36593593; 37004249
Phenotypes for gene: PLCZ1 were set to Spermatogenic failure 17, MIM# 617214
Review for gene: PLCZ1 was set to GREEN
Added comment: i) PMID:26721930- homozygous missense variant (I489F) in 2 Tunisian brothers with infertility due to oocyte activation failure.
ii) PMID:31463947- 3 homozygous variants (C196X, S350P, L246F) in 4 Chinese men from 3 consanguineous families with SPGF17 and total fertilization failure of oocytes after intracytoplasmic sperm injection.
iii) PMID: 36593593- compound heterozygosity for splice site and missense variants (c.1174+3A-C and N425S in case 2; c.136-1G-C and G453D in case 3) in 2 unrelated Chinese men with infertility due to acrosomal abnormalities and total fertilization failure.
iv) PMID: 37004249- previously reported homozygous variant (C196X) in two unrelated men with infertility due to total fertilization failure
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.6 PLCZ1 Zornitza Stark Marked gene: PLCZ1 as ready
Infertility and Recurrent Pregnancy Loss v0.6 PLCZ1 Zornitza Stark Gene: plcz1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.6 PLCZ1 Zornitza Stark Phenotypes for gene: PLCZ1 were changed from #MIM:617214 to Spermatogenic failure 17, MIM# 617214
Infertility and Recurrent Pregnancy Loss v0.5 PLCZ1 Zornitza Stark Classified gene: PLCZ1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.5 PLCZ1 Zornitza Stark Gene: plcz1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.4 PLCZ1 Zornitza Stark reviewed gene: PLCZ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 17, MIM# 617214; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.342 EXO1 Zornitza Stark Marked gene: EXO1 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.342 EXO1 Zornitza Stark Gene: exo1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.342 EXO1 Zornitza Stark Classified gene: EXO1 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.342 EXO1 Zornitza Stark Gene: exo1 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.341 EXO1 Zornitza Stark gene: EXO1 was added
gene: EXO1 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: EXO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EXO1 were set to 39595984; 32772095; 36385415
Phenotypes for gene: EXO1 were set to Primary ovarian failure, MONDO:0005387, EXO1-related
Review for gene: EXO1 was set to GREEN
Added comment: 1. PMID:39595984- heterozygous nonsense variant (p.Glu829Ter) in an European female with diminished ovarian reserve
2. PMID:32772095- heterozygous missense variant (p.Thr52Ser) in a Chinese patient with POI, which impaired the meiotic process in budding yeast cells and analysis of transfected HEK293 cells demonstrated impaired efficiency of homologous recombination repair for DNA double-stranded breaks with the mutant compared to wildtype EXO1
3. PMID:36385415- heterozygous nonsense variant (p.Tyr742Ter) in a case (C23) with recurrent pregnancy loss (RPL), primary infertility (PI), recurrent implantation failure (RIF)
Sources: Literature
Mendeliome v1.2421 EXO1 Zornitza Stark Marked gene: EXO1 as ready
Mendeliome v1.2421 EXO1 Zornitza Stark Gene: exo1 has been classified as Green List (High Evidence).
Mendeliome v1.2421 EXO1 Zornitza Stark Classified gene: EXO1 as Green List (high evidence)
Mendeliome v1.2421 EXO1 Zornitza Stark Gene: exo1 has been classified as Green List (High Evidence).
Mendeliome v1.2420 EXO1 Zornitza Stark gene: EXO1 was added
gene: EXO1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EXO1 were set to 39595984; 32772095; 36385415
Phenotypes for gene: EXO1 were set to Primary ovarian failure, MONDO:0005387, EXO1-related
Review for gene: EXO1 was set to GREEN
Added comment: 1. PMID:39595984- heterozygous nonsense variant (p.Glu829Ter) in an European female with diminished ovarian reserve
2. PMID:32772095- heterozygous missense variant (p.Thr52Ser) in a Chinese patient with POI, which impaired the meiotic process in budding yeast cells and analysis of transfected HEK293 cells demonstrated impaired efficiency of homologous recombination repair for DNA double-stranded breaks with the mutant compared to wildtype EXO1
3. PMID:36385415- heterozygous nonsense variant (p.Tyr742Ter) in a case (C23) with recurrent pregnancy loss (RPL), primary infertility (PI), recurrent implantation failure (RIF)
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.4 EXO1 Zornitza Stark Marked gene: EXO1 as ready
Infertility and Recurrent Pregnancy Loss v0.4 EXO1 Zornitza Stark Gene: exo1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.4 EXO1 Zornitza Stark Phenotypes for gene: EXO1 were changed from MONDO:0005387 to Primary ovarian failure, MONDO:0005387, EXO1-related
Infertility and Recurrent Pregnancy Loss v0.3 EXO1 Zornitza Stark Classified gene: EXO1 as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.3 EXO1 Zornitza Stark Gene: exo1 has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.2 EXO1 Zornitza Stark reviewed gene: EXO1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary ovarian failure, MONDO:0005387, EXO1-related; Mode of inheritance: None
Mendeliome v1.2419 DDX3Y Zornitza Stark Marked gene: DDX3Y as ready
Mendeliome v1.2419 DDX3Y Zornitza Stark Gene: ddx3y has been classified as Green List (High Evidence).
Mendeliome v1.2419 DDX3Y Zornitza Stark Classified gene: DDX3Y as Green List (high evidence)
Mendeliome v1.2419 DDX3Y Zornitza Stark Gene: ddx3y has been classified as Green List (High Evidence).
Mendeliome v1.2418 DDX3Y Zornitza Stark gene: DDX3Y was added
gene: DDX3Y was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: DDX3Y was set to Other
Publications for gene: DDX3Y were set to 36997603
Phenotypes for gene: DDX3Y were set to Azoospermia, MONDO:0100459, DDX3Y-related
Review for gene: DDX3Y was set to GREEN
Added comment: PMID:36997603- Four (3 German, 1 Estonian) unrelated men with non-obstructive azoospermia carrying different LOF variants- absent in the gnomAD database (v2.1.1), abrogate at least the sequence of the C-terminal helicase domain, and are predicted to lead to degradation of the transcripts by nonsense-mediated decay. All four patients shared histological phenotype of Sertoli cell-only (SCO), reduced testicular volume, and had elevated FSH upon primary or later presentation indicative of spermatogenic failure.

Mode of inheritance: Y-linked
Sources: Expert Review
Infertility and Recurrent Pregnancy Loss v0.2 DDX3Y Zornitza Stark Marked gene: DDX3Y as ready
Infertility and Recurrent Pregnancy Loss v0.2 DDX3Y Zornitza Stark Gene: ddx3y has been classified as Green List (High Evidence).
Infertility and Recurrent Pregnancy Loss v0.2 DDX3Y Zornitza Stark Phenotypes for gene: DDX3Y were changed from MONDO:0100459 to Azoospermia, MONDO:0100459, DDX3Y-related
Infertility and Recurrent Pregnancy Loss v0.1 DDX3Y Zornitza Stark Classified gene: DDX3Y as Green List (high evidence)
Infertility and Recurrent Pregnancy Loss v0.1 DDX3Y Zornitza Stark Gene: ddx3y has been classified as Green List (High Evidence).
Mendeliome v1.2417 CFAP221 Achchuthan Shanmugasundram reviewed gene: CFAP221: Rating: AMBER; Mode of pathogenicity: None; Publications: 31636325, 39362668; Phenotypes: primary ciliary dyskinesia, MONDO:0016575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Infertility and Recurrent Pregnancy Loss v0.0 TEX11 Jasmine Chew gene: TEX11 was added
gene: TEX11 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: TEX11 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TEX11 were set to 25970010; 29661171; 34621296; 37124723
Phenotypes for gene: TEX11 were set to #MIM:309120
Review for gene: TEX11 was set to GREEN
Added comment: i) PMID:25970010- hemizygous variants in 7 out of of 289 azoospermic men, including a 90kb exonic deletion (Ex10-12) in 2 European men, 2 missense variants in 2 European/German men, and 3 splice variants in two white and one Arabic men.

ii) PMID: 29661171 (2018)- a novel hemizygous missense variant (W856C) in two brothers with azoospermia (absent in the mother- ?can it be gonadal mosaicism). Their testicular biopsy revealed meiotic arrest and no post-meiotic round spermatids and mature spermatozoa were observed.

iii) PMID: 34621296 (2021)- seven novel hemizygous variants in three familial (one missense, two splice) and four NOA-affected sporadic (three frameshift, one nonsense) cases

iv) PMID: 37124723 (2023)- three novel hemizygous variants ( p.R105*, p.K143Q, and p.G859R) in three unrelated NOA males and their histological analysis of testicular biopsy specimens revealed thicker basement membrane of the seminiferous tubules and poorly developed spermatocytes.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.0 SPAG6 Jasmine Chew gene: SPAG6 was added
gene: SPAG6 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: SPAG6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPAG6 were set to 35232447; 38073178; 32124190
Phenotypes for gene: SPAG6 were set to MONDO:0004983
Review for gene: SPAG6 was set to GREEN
Added comment: i) PMID: 35232447- two homozygous variants (F1 II-1: p. A103D; F2 II-1:p. K196Sfs*6) in two unrelated Han Chinese men with nonsyndromic asthenoteratozoospermia with severe multiple morphological abnormalities of the sperm flagella. Immunostaining and WB showed lower SPAG6 expression in spermatozoa of both affected males. The couple with the missense variant as able to conceive successfully after undergoing ICSI.
ii) PMID: 38073178- a homozygous missense p.R310W in three brothers (two brothers with both asthenozoospermia and oligozoospermia, third brother with azoospermia)
iii) PMID: 32124190- a novel compound heterozygous variant (c.143_145del: p.48_49del, c.585delA: p.Lys196Serfs*6) in an infertile PCD patient with severe with asthenoteratozoospermia, presented with morphological defects of sperm flagella and lower mRNA and protein expression in mutant sperms.
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.0 SEPT12 Jasmine Chew gene: SEPT12 was added
gene: SEPT12 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: SEPT12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SEPT12 were set to 22479503; 22275165; 35547809
Phenotypes for gene: SEPT12 were set to #MIM:614822
Review for gene: SEPT12 was set to GREEN
Added comment: i) PMID: 22479503- A homozygous truncating variant (c.474 G>A) in 15 unrelated infertile men and 9 of them had teratozoospermia (88 to 99% of abnormal sperm);Transfection studies also showed that the mutant SEPT12 disrupted filament formation of wildtype SEPT12 in a dose-dependent manner.
ii) PMID:22275165- Two heterozygous missense variants (T89M and D197N) in a man with asthenoteratozoospermia and another man with oligoasthenozoospermia. Functional analysis demonstrated that both mutations adversely affected filament formation of wildtype SEPT12 in a dose-dependent manner.
iii) PMID: 35547809- A heterozygous missense variant (p.Cys24Ter) in the male partner of a patient couple, who had a previous fertilization failure (FF) after intracytoplasmic sperm injection (ICSI) and became pregnant after ICSI together with artificial oocyte activation (AOA). Their Septin12 knockout mice study also showed that Septin12 -/- male mice are infertile with reduced sperm counts and abnormal sperm morphology but male Septin12 +/− mice are fertile. This observation contradicted with the previous studies showed that male Septin12 +/− chimeric mice are infertile (Lin et al., 2009, PMID: 19359518). The main difference is that the Septin12 +/− chimeric mice were generated in Lin et al., 2009 (PMID: 19359518) was by blastocyst injection of Septin12 +/− embryonic stem cells (ESCs), while their Septin12 +/− founder mice were established by CRISPR/Cas9 mediated gene editing in the zygote. The quality of injected Septin12 +/− ESCs might affect the experimental result.

Note:#MIM:614822 stated as AD, but there's evidence suggesting AR
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.0 PLCZ1 Jasmine Chew changed review comment from: i) PMID:26721930- homozygous missense variant (I489F) in 2 Tunisian brothers with infertility due to oocyte activation failure.
ii) PMID:31463947- 3 homozygous variants (C196X, S350P, L246F) in 4 Chinese men from 3 consanguineous families with SPGF17 and total fertilization failure of oocytes after intracytoplasmic sperm injection.
iii) PMID: 36593593- compound heterozygosity for splice site and missense variants (c.1174+3A-C and N425S in case 2; c.136-1G-C and G453D in case 3) in 2 unrelated Chinese men with infertility due to acrosomal abnormalities and total fertilization failure.
iv) PMID: 37004249- previously reported homozygous variant (C196X) in two unrelated men with infertility due to total fertilization failure
Sources: Literature; to: i) PMID:26721930- homozygous missense variant (I489F) in 2 Tunisian brothers with infertility due to oocyte activation failure.
ii) PMID:31463947- 3 homozygous variants (C196X, S350P, L246F) in 4 Chinese men from 3 consanguineous families with SPGF17 and total fertilization failure of oocytes after intracytoplasmic sperm injection.
iii) PMID: 36593593- compound heterozygosity for splice site and missense variants (c.1174+3A-C and N425S in case 2; c.136-1G-C and G453D in case 3) in 2 unrelated Chinese men with infertility due to acrosomal abnormalities and total fertilization failure.
iv) PMID: 37004249- previously reported homozygous variant (C196X) in two unrelated men with infertility due to total fertilization failure
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.0 PLCZ1 Jasmine Chew changed review comment from: i) PMID:26721930- homozygous missense variant (I489F) in 2 Tunisian brothers with infertility due to oocyte activation failure.
ii) PMID:31463947- 3 homozygous variants (C196X, S350P, L246F) in 4 Chinese men from 3 consanguineous families with SPGF17 and total fertilization failure of oocytes after intracytoplasmic sperm injection.
iii) PMID: 36593593 (2023)- compound heterozygosity for splice site and missense variants (c.1174+3A-C and N425S in case 2; c.136-1G-C and G453D in case 3) in 2 unrelated Chinese men with infertility due to acrosomal abnormalities and total fertilization failure.
iv) PMID: 37004249 (2023)- previously reported homozygous variant (C196X) in two unrelated men with infertility due to total fertilization failure
Sources: Literature; to: i) PMID:26721930- homozygous missense variant (I489F) in 2 Tunisian brothers with infertility due to oocyte activation failure.
ii) PMID:31463947- 3 homozygous variants (C196X, S350P, L246F) in 4 Chinese men from 3 consanguineous families with SPGF17 and total fertilization failure of oocytes after intracytoplasmic sperm injection.
iii) PMID: 36593593- compound heterozygosity for splice site and missense variants (c.1174+3A-C and N425S in case 2; c.136-1G-C and G453D in case 3) in 2 unrelated Chinese men with infertility due to acrosomal abnormalities and total fertilization failure.
iv) PMID: 37004249- previously reported homozygous variant (C196X) in two unrelated men with infertility due to total fertilization failure
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.0 PLCZ1 Jasmine Chew gene: PLCZ1 was added
gene: PLCZ1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: PLCZ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLCZ1 were set to 26721930; 31463947; 36593593; 37004249
Phenotypes for gene: PLCZ1 were set to #MIM:617214
Review for gene: PLCZ1 was set to GREEN
Added comment: i) PMID:26721930- homozygous missense variant (I489F) in 2 Tunisian brothers with infertility due to oocyte activation failure.
ii) PMID:31463947- 3 homozygous variants (C196X, S350P, L246F) in 4 Chinese men from 3 consanguineous families with SPGF17 and total fertilization failure of oocytes after intracytoplasmic sperm injection.
iii) PMID: 36593593 (2023)- compound heterozygosity for splice site and missense variants (c.1174+3A-C and N425S in case 2; c.136-1G-C and G453D in case 3) in 2 unrelated Chinese men with infertility due to acrosomal abnormalities and total fertilization failure.
iv) PMID: 37004249 (2023)- previously reported homozygous variant (C196X) in two unrelated men with infertility due to total fertilization failure
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.0 EXO1 Jasmine Chew gene: EXO1 was added
gene: EXO1 was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: EXO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EXO1 were set to 39595984; 32772095; 36385415
Phenotypes for gene: EXO1 were set to MONDO:0005387
Review for gene: EXO1 was set to GREEN
Added comment: 1. PMID:39595984- heterozygous nonsense variant (p.Glu829Ter) in an European female with diminished ovarian reserve
2. PMID:32772095- heterozygous missense variant (p.Thr52Ser) in a Chinese patient with POI, which impaired the meiotic process in budding yeast cells and analysis of transfected HEK293 cells demonstrated impaired efficiency of homologous recombination repair for DNA double-stranded breaks with the mutant compared to wildtype EXO1
3. PMID:36385415- heterozygous nonsense variant (p.Tyr742Ter) in a case (C23) with recurrent pregnancy loss (RPL), primary infertility (PI), recurrent implantation failure (RIF)
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.0 DDX3Y Jasmine Chew changed review comment from: PMID:36997603- 4 (3 German, 1 Estonian) unrelated men with non-obstructive azoospermia carrying different LOF variants- absent in the gnomAD database (v2.1.1), abrogate at least the sequence of the C-terminal helicase domain, and are predicted to lead to degradation of the transcripts by nonsense-mediated decay. All four patients shared histological phenotype of Sertoli cell-only (SCO), reduced testicular volume, and had elevated FSH upon primary or later presentation indicative of spermatogenic failure.

Mode of inheritance: Y-linked
Sources: Literature; to: PMID:36997603- Four (3 German, 1 Estonian) unrelated men with non-obstructive azoospermia carrying different LOF variants- absent in the gnomAD database (v2.1.1), abrogate at least the sequence of the C-terminal helicase domain, and are predicted to lead to degradation of the transcripts by nonsense-mediated decay. All four patients shared histological phenotype of Sertoli cell-only (SCO), reduced testicular volume, and had elevated FSH upon primary or later presentation indicative of spermatogenic failure.

Mode of inheritance: Y-linked
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.0 DDX3Y Jasmine Chew gene: DDX3Y was added
gene: DDX3Y was added to Infertility and Pregnancy Loss. Sources: Literature
Mode of inheritance for gene: DDX3Y was set to Other
Publications for gene: DDX3Y were set to 36997603
Phenotypes for gene: DDX3Y were set to MONDO:0100459
Review for gene: DDX3Y was set to GREEN
Added comment: PMID:36997603- 4 (3 German, 1 Estonian) unrelated men with non-obstructive azoospermia carrying different LOF variants- absent in the gnomAD database (v2.1.1), abrogate at least the sequence of the C-terminal helicase domain, and are predicted to lead to degradation of the transcripts by nonsense-mediated decay. All four patients shared histological phenotype of Sertoli cell-only (SCO), reduced testicular volume, and had elevated FSH upon primary or later presentation indicative of spermatogenic failure.

Mode of inheritance: Y-linked
Sources: Literature
Congenital Diarrhoea v1.14 EZR Zornitza Stark Marked gene: EZR as ready
Congenital Diarrhoea v1.14 EZR Zornitza Stark Gene: ezr has been classified as Red List (Low Evidence).
Congenital Diarrhoea v1.14 EZR Zornitza Stark gene: EZR was added
gene: EZR was added to Congenital Diarrhoea. Sources: Literature
Mode of inheritance for gene: EZR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EZR were set to 40137958
Phenotypes for gene: EZR were set to Congenital enteropathy, MONDO:0009173, EZR-related
Review for gene: EZR was set to RED
Added comment: Homozygous LoF variant c. 356dup (p. Glu120*) - present in gnomAD v4.1 (rare enough for AR condition) Infant from consanguineous parents with intractable diarrhea and failure to thrive. A supportive functional assay showing the variant is predicted to result in NMD was conducted. No other reports of other variants in this gene to support this gene disease association as of yet.
Sources: Literature
Mendeliome v1.2417 EZR Zornitza Stark Marked gene: EZR as ready
Mendeliome v1.2417 EZR Zornitza Stark Gene: ezr has been classified as Red List (Low Evidence).
Mendeliome v1.2417 EZR Zornitza Stark Classified gene: EZR as Red List (low evidence)
Mendeliome v1.2417 EZR Zornitza Stark Gene: ezr has been classified as Red List (Low Evidence).
Mendeliome v1.2416 IDH3G Zornitza Stark Marked gene: IDH3G as ready
Mendeliome v1.2416 IDH3G Zornitza Stark Gene: idh3g has been classified as Green List (High Evidence).
Mendeliome v1.2416 IDH3G Zornitza Stark Classified gene: IDH3G as Green List (high evidence)
Mendeliome v1.2416 IDH3G Zornitza Stark Gene: idh3g has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.158 IDH3G Zornitza Stark Marked gene: IDH3G as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.158 IDH3G Zornitza Stark Gene: idh3g has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.158 IDH3G Zornitza Stark Classified gene: IDH3G as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.158 IDH3G Zornitza Stark Gene: idh3g has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.157 C19orf44 Zornitza Stark Marked gene: C19orf44 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.157 C19orf44 Zornitza Stark Gene: c19orf44 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.157 C19orf44 Zornitza Stark Classified gene: C19orf44 as Green List (high evidence)
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.157 C19orf44 Zornitza Stark Gene: c19orf44 has been classified as Green List (High Evidence).
Mendeliome v1.2415 C19orf44 Zornitza Stark Marked gene: C19orf44 as ready
Mendeliome v1.2415 C19orf44 Zornitza Stark Gene: c19orf44 has been classified as Green List (High Evidence).
Mendeliome v1.2415 C19orf44 Zornitza Stark Classified gene: C19orf44 as Green List (high evidence)
Mendeliome v1.2415 C19orf44 Zornitza Stark Gene: c19orf44 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1822 LMBR1 Zornitza Stark Marked gene: LMBR1 as ready
Prepair 1000+ v1.1822 LMBR1 Zornitza Stark Gene: lmbr1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1822 LMBR1 Zornitza Stark Phenotypes for gene: LMBR1 were changed from Acheiropody, 200500 (3) to Acheiropody, MIM #200500
Prepair 1000+ v1.1821 LMBR1 Zornitza Stark Publications for gene: LMBR1 were set to
Mitochondrial disease v0.971 TIMM29 Zornitza Stark Marked gene: TIMM29 as ready
Mitochondrial disease v0.971 TIMM29 Zornitza Stark Gene: timm29 has been classified as Red List (Low Evidence).
Mitochondrial disease v0.971 TIMM29 Zornitza Stark gene: TIMM29 was added
gene: TIMM29 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: TIMM29 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TIMM29 were set to 40022150
Phenotypes for gene: TIMM29 were set to Sengers syndrome MONDO:0008922, TIMM29-related
Review for gene: TIMM29 was set to RED
Added comment: One large Arab family presenting with a range of clinical and biochemical phenotypes suggestive of Sengers Syndrome. Biallelic p.Trp172Arg was identified that segregated through the family - this variant is absent from gnomADv4.1 Knockdown drosophillia assay recapitulated the phenotype and pathology observed in the cohort of senger syndrome affected patients.
Sources: Literature
Mendeliome v1.2414 TIMM29 Zornitza Stark Marked gene: TIMM29 as ready
Mendeliome v1.2414 TIMM29 Zornitza Stark Gene: timm29 has been classified as Red List (Low Evidence).
Mendeliome v1.2414 TIMM29 Zornitza Stark Classified gene: TIMM29 as Red List (low evidence)
Mendeliome v1.2414 TIMM29 Zornitza Stark Gene: timm29 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.1820 LMBR1 Kate Scarff reviewed gene: LMBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11090342, 10780921, 33863876; Phenotypes: Acheiropody, MIM #200500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1820 LAMC2 Zornitza Stark Phenotypes for gene: LAMC2 were changed from Epidermolysis bullosa, junctional, Herlitz type, MIM#619785; Epidermolysis bullosa, junctional, non-Herlitz type, MIM#619786 to Epidermolysis bullosa, junctional 3B, severe MIM #619786; Epidermolysis bullosa, junctional 3A, intermediate MIM #619785
Prepair 1000+ v1.1819 LAMC2 Zornitza Stark Publications for gene: LAMC2 were set to
Prepair 1000+ v1.1818 LAMC2 Kate Scarff reviewed gene: LAMC2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32017015, 11810295, 24533970, 20301304; Phenotypes: Epidermolysis bullosa, junctional 3B, severe MIM #619786, Epidermolysis bullosa, junctional 3A, intermediate MIM #619785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2413 TIMM29 Sangavi Sivagnanasundram gene: TIMM29 was added
gene: TIMM29 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TIMM29 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TIMM29 were set to 40022150
Phenotypes for gene: TIMM29 were set to Sengers syndrome MONDO:0008922, TIMM29-related
Review for gene: TIMM29 was set to RED
Added comment: One large Arab family presenting with a range of clinical and biochemical phenotypes suggestive of Sengers Syndrome.
Biallelic p.Trp172Arg was identified that segregated through the family - this variant is absent from gnomADv4.1
Knockdown drosophillia assay recapitulated the phenotype and pathology observed in the cohort of senger syndrome affected patients.
Sources: Literature
Prepair 1000+ v1.1818 TSPAN7 Michelle Torres reviewed gene: TSPAN7: Rating: AMBER; Mode of pathogenicity: None; Publications: 26350204, 36625203; Phenotypes: Intellectual developmental disorder, X-linked 58, MIM #300210, MONDO:0010266; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.2413 C19orf44 Sangavi Sivagnanasundram edited their review of gene: C19orf44: Changed phenotypes: Late onset retinal dystrophy, MONDO:0019118
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.156 C19orf44 Sangavi Sivagnanasundram gene: C19orf44 was added
gene: C19orf44 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: C19orf44 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C19orf44 were set to 40079362
Phenotypes for gene: C19orf44 were set to Late onset retinal dystrophy, MONDO:0019118
Review for gene: C19orf44 was set to GREEN
Added comment: 5 biallelic LoF variants were identified in 11 unrelated families of Jewish or Israeli ancestry. All affected individuals present with a form of retinal disorder including perifoveal chorioretinal atrophy and electroretinographic features of rod-cone degeneration.
All 5 variants were present in gnomAD v4.1 with varying AF (p.Ser325PhefsTer16 being the most common).
Sources: Literature
Mendeliome v1.2413 C19orf44 Sangavi Sivagnanasundram gene: C19orf44 was added
gene: C19orf44 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C19orf44 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C19orf44 were set to 40079362
Phenotypes for gene: C19orf44 were set to Late onset retinal dystrophy; MONDO:0019118
Review for gene: C19orf44 was set to GREEN
Added comment: 5 biallelic LoF variants were identified in 11 unrelated families of Jewish or Israeli ancestry. All affected individuals present with a form of retinal disorder including perifoveal chorioretinal atrophy and electroretinographic features of rod-cone degeneration.
All 5 variants were present in gnomAD v4.1 with varying AF (p.Ser325PhefsTer16 being the most common).
Sources: Literature
Infertility and Recurrent Pregnancy Loss v0.0 Zornitza Stark Added Panel Infertility and Pregnancy Loss
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.156 IDH3G Sangavi Sivagnanasundram gene: IDH3G was added
gene: IDH3G was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature
Mode of inheritance for gene: IDH3G was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IDH3G were set to 40119724
Phenotypes for gene: IDH3G were set to X-linked retinitis pigmentosa, MONDO:0019200
Review for gene: IDH3G was set to GREEN
Added comment: PMID: 40119724
5 unrelated male probands with retinal pigmentosa (RP) identifed with hemizygous variants in IDH3G and was shown to segregate with disease in some families.
Sources: Literature
Mendeliome v1.2413 IDH3G Sangavi Sivagnanasundram gene: IDH3G was added
gene: IDH3G was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IDH3G was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IDH3G were set to 40119724
Phenotypes for gene: IDH3G were set to X-linked retinitis pigmentosa, MONDO:0019200
Review for gene: IDH3G was set to GREEN
Added comment: PMID: 40119724
5 unrelated male probands with retinal pigmentosa (RP) identifed with hemizygous variants in IDH3G and was shown to segregate with disease in some families.
Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.45 MYH10 Zornitza Stark changed review comment from: Three individuals reported with coloboma and ptosis as features, pheno expansion.
Sources: Literature; to: Three individuals reported with coloboma and ptosis as features, pheno expansion.
Sources: Literature
Mendeliome v1.2413 TFRC Zornitza Stark Phenotypes for gene: TFRC were changed from Immunodeficiency 46, MIM# 616740; T cells: normal number, poor proliferation; B cells: normal number, low memory B cells; recurrent infections, neutorpaenia; thrombocytopaenia to TFRC-related combined immunodeficiency MONDO:0014760; Immunodeficiency 46, MIM# 616740; T cells: normal number, poor proliferation; B cells: normal number, low memory B cells; recurrent infections, neutorpaenia; thrombocytopaenia
Mendeliome v1.2412 TFRC Zornitza Stark Classified gene: TFRC as Green List (high evidence)
Mendeliome v1.2412 TFRC Zornitza Stark Gene: tfrc has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.118 TFRC Zornitza Stark Phenotypes for gene: TFRC were changed from Immunodeficiency 46, MIM# 616740; T cells: normal number, poor proliferation; B cells: normal number, low memory B cells; recurrent infections, neutorpaenia; thrombocytopaenia to Immunodeficiency 46, MIM# 616740; TFRC-related combined immunodeficiency MONDO:0014760
Combined Immunodeficiency v1.117 TFRC Zornitza Stark Publications for gene: TFRC were set to 26642240
Combined Immunodeficiency v1.116 TFRC Zornitza Stark Classified gene: TFRC as Green List (high evidence)
Combined Immunodeficiency v1.116 TFRC Zornitza Stark Gene: tfrc has been classified as Green List (High Evidence).
Mendeliome v1.2411 TAX1BP3 Zornitza Stark Marked gene: TAX1BP3 as ready
Mendeliome v1.2411 TAX1BP3 Zornitza Stark Gene: tax1bp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2411 TAX1BP3 Zornitza Stark Classified gene: TAX1BP3 as Amber List (moderate evidence)
Mendeliome v1.2411 TAX1BP3 Zornitza Stark Gene: tax1bp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2410 TAX1BP3 Zornitza Stark gene: TAX1BP3 was added
gene: TAX1BP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TAX1BP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAX1BP3 were set to 39963794
Phenotypes for gene: TAX1BP3 were set to Familial cardiomyopathy, MONDO:0005217, TAX1BP3-related
Review for gene: TAX1BP3 was set to AMBER
Added comment: Biallelic variants (1 x del, 1 x missense) in TAX1BP3 cause a novel autosomal recessive form of arrhythmogenic cardiomyopathy. One family only, but 3 affected sibs had the bialleic variants which were absent in an unaffected sister. Carrier parents were normal. Experimental work on patient-derived induced pluripotent stem cell cardiac myocytes and a knockout mouse showed that show loss of TAX1BP3 causes calcium dysregulation in cardiomyocytes, a known mechanism for arrhythmia. AMBER until more case level data evolves.
Sources: Literature
Arrhythmogenic Cardiomyopathy v0.70 TAX1BP3 Zornitza Stark Marked gene: TAX1BP3 as ready
Arrhythmogenic Cardiomyopathy v0.70 TAX1BP3 Zornitza Stark Gene: tax1bp3 has been classified as Amber List (Moderate Evidence).
Arrhythmogenic Cardiomyopathy v0.70 TAX1BP3 Zornitza Stark Phenotypes for gene: TAX1BP3 were changed from arrhythmogenic cardiomyopathy to Familial cardiomyopathy, MONDO:0005217, TAX1BP3-related; arrhythmogenic cardiomyopathy
Arrhythmogenic Cardiomyopathy v0.69 TAX1BP3 Zornitza Stark Classified gene: TAX1BP3 as Amber List (moderate evidence)
Arrhythmogenic Cardiomyopathy v0.69 TAX1BP3 Zornitza Stark Gene: tax1bp3 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v1.49 CFAP54 Zornitza Stark Publications for gene: CFAP54 were set to PMID: 26224312; 36593121; 37725231
Ciliary Dyskinesia v1.48 CFAP54 Zornitza Stark Classified gene: CFAP54 as Green List (high evidence)
Ciliary Dyskinesia v1.48 CFAP54 Zornitza Stark Gene: cfap54 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.47 CFAP54 Zornitza Stark edited their review of gene: CFAP54: Added comment: PMID:39362668 reported four unrelated patients aged between 2 and 25 years old, three of whom were compound heterozygous and one homozygous for pathogenic variants in CFAP54. All reported chronic respiratory symptoms and all three patients for whom data was available had bronchiectasis. Two patients reported neonatal chest symptoms, one did not and data was missing for the other patient. No data were available on fertility status. In keeping with other C1d mutations they all had situs solitus and normal EM and HSVMA in those where data were available, but studies of in vitro ciliary transport performed in two subjects found that this was impaired in both.; Changed rating: GREEN; Changed publications: 36593121, 37725231, 39362668
Mendeliome v1.2409 CFAP54 Zornitza Stark Phenotypes for gene: CFAP54 were changed from Spermatogenic failure 98, MIM# 621124; Hydrocephalus, male infertility, mucus accumulation to Ciliary dyskinesia, primary, 54, MIM:621125; Spermatogenic failure 98, MIM# 621124; Hydrocephalus, male infertility, mucus accumulation
Mendeliome v1.2408 CFAP54 Zornitza Stark Publications for gene: CFAP54 were set to 26224312; 36593121
Mendeliome v1.2407 CFAP54 Zornitza Stark Classified gene: CFAP54 as Green List (high evidence)
Mendeliome v1.2407 CFAP54 Zornitza Stark Gene: cfap54 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.45 MYH10 Zornitza Stark Marked gene: MYH10 as ready
Anophthalmia_Microphthalmia_Coloboma v1.45 MYH10 Zornitza Stark Gene: myh10 has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.45 MYH10 Zornitza Stark Classified gene: MYH10 as Amber List (moderate evidence)
Anophthalmia_Microphthalmia_Coloboma v1.45 MYH10 Zornitza Stark Gene: myh10 has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.44 MYH10 Zornitza Stark gene: MYH10 was added
gene: MYH10 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: MYH10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH10 were set to 40044823
Phenotypes for gene: MYH10 were set to Neurodevelopmental disorder, MONDO:0700092, MYH10-related
Review for gene: MYH10 was set to AMBER
Added comment: Three individuals reported with coloboma and ptosis as features, pheno expansion.
Sources: Literature
Congenital Heart Defect v0.436 MED16 Zornitza Stark Marked gene: MED16 as ready
Congenital Heart Defect v0.436 MED16 Zornitza Stark Gene: med16 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.436 MED16 Zornitza Stark Classified gene: MED16 as Green List (high evidence)
Congenital Heart Defect v0.436 MED16 Zornitza Stark Gene: med16 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.435 MED16 Zornitza Stark gene: MED16 was added
gene: MED16 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: MED16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED16 were set to 40081376
Phenotypes for gene: MED16 were set to Neurodevelopmental disorder, MONDO:0700092, MED16-related
Review for gene: MED16 was set to GREEN
Added comment: 18 families reported with DD/ID +/- multiple congenital anomalies including CHD (predominantly Tetralogy of Fallot).
Sources: Literature
Mendeliome v1.2406 EZR Sangavi Sivagnanasundram gene: EZR was added
gene: EZR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EZR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EZR were set to 40137958
Phenotypes for gene: EZR were set to Congenital enteropathy, MONDO:0009173
Review for gene: EZR was set to RED
Added comment: Homozygous LoF variant c. 356dup (p. Glu120*) - present in gnomAD v4.1 (rare enough for AR condition)
Infant from consanguineous parents with intractable diarrhea and failure to thrive.
A supportive functional assay showing the variant is predicted to result in NMD was conducted.
No other reports of other variants in this gene to support this gene disease association as of yet.
Sources: Literature
Clefting disorders v0.262 MED16 Zornitza Stark Marked gene: MED16 as ready
Clefting disorders v0.262 MED16 Zornitza Stark Gene: med16 has been classified as Green List (High Evidence).
Clefting disorders v0.262 MED16 Zornitza Stark Classified gene: MED16 as Green List (high evidence)
Clefting disorders v0.262 MED16 Zornitza Stark Gene: med16 has been classified as Green List (High Evidence).
Clefting disorders v0.261 MED16 Zornitza Stark gene: MED16 was added
gene: MED16 was added to Clefting disorders. Sources: Literature
Mode of inheritance for gene: MED16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED16 were set to 40081376
Phenotypes for gene: MED16 were set to Neurodevelopmental disorder, MONDO:0700092, MED16-related
Review for gene: MED16 was set to GREEN
Added comment: 18 families reported with bi-allelic variants in this gene with DD/ID +/- multiple congenital anomalies, including cleft palate in multiple individuals.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.96 MED16 Zornitza Stark Phenotypes for gene: MED16 were changed from complex neurodevelopmental disorder MONDO:0100038 to Neurodevelopmental disorder, MONDO:0700092, MED16-related
Intellectual disability syndromic and non-syndromic v1.95 MED16 Zornitza Stark Publications for gene: MED16 were set to
Intellectual disability syndromic and non-syndromic v1.94 MED16 Zornitza Stark reviewed gene: MED16: Rating: GREEN; Mode of pathogenicity: None; Publications: 40081376; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, MED16-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2406 CELF4 Zornitza Stark Marked gene: CELF4 as ready
Mendeliome v1.2406 CELF4 Zornitza Stark Gene: celf4 has been classified as Green List (High Evidence).
Mendeliome v1.2406 CELF4 Zornitza Stark Classified gene: CELF4 as Green List (high evidence)
Mendeliome v1.2406 CELF4 Zornitza Stark Gene: celf4 has been classified as Green List (High Evidence).
Mendeliome v1.2405 CELF4 Zornitza Stark gene: CELF4 was added
gene: CELF4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CELF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELF4 were set to 40108438
Phenotypes for gene: CELF4 were set to Neurodevelopmental disorder, MONDO:0700092, CELF4-related
Review for gene: CELF4 was set to GREEN
Added comment: 15 individuals with de novo missense variants clustering in the N-terminal reported, LoF is the likely mechanism. Most individuals presented with neurodevelopmental disorders including global developmental delay/intellectual disability (11/14), seizures (9/15) and overweight/obesity (10/14). Clinical features are similar to the reported celf4-mouse mutant phenotype.
Sources: Literature
Severe early-onset obesity v1.15 CELF4 Zornitza Stark Marked gene: CELF4 as ready
Severe early-onset obesity v1.15 CELF4 Zornitza Stark Gene: celf4 has been classified as Green List (High Evidence).
Severe early-onset obesity v1.15 CELF4 Zornitza Stark Classified gene: CELF4 as Green List (high evidence)
Severe early-onset obesity v1.15 CELF4 Zornitza Stark Gene: celf4 has been classified as Green List (High Evidence).
Severe early-onset obesity v1.14 CELF4 Zornitza Stark gene: CELF4 was added
gene: CELF4 was added to Severe early-onset obesity. Sources: Literature
Mode of inheritance for gene: CELF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELF4 were set to 40108438
Phenotypes for gene: CELF4 were set to Neurodevelopmental disorder, MONDO:0700092, CELF4-related
Review for gene: CELF4 was set to GREEN
Added comment: 15 individuals with de novo missense variants clustering in the N-terminal reported, LoF is the likely mechanism. Most individuals presented with neurodevelopmental disorders including global developmental delay/intellectual disability (11/14), seizures (9/15) and overweight/obesity (10/14). Clinical features are similar to the reported celf4-mouse mutant phenotype.
Sources: Literature
Genetic Epilepsy v1.124 CELF4 Zornitza Stark Marked gene: CELF4 as ready
Genetic Epilepsy v1.124 CELF4 Zornitza Stark Gene: celf4 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.124 CELF4 Zornitza Stark Classified gene: CELF4 as Green List (high evidence)
Genetic Epilepsy v1.124 CELF4 Zornitza Stark Gene: celf4 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.123 CELF4 Zornitza Stark gene: CELF4 was added
gene: CELF4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CELF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELF4 were set to 40108438
Phenotypes for gene: CELF4 were set to Neurodevelopmental disorder, MONDO:0700092, CELF4-related
Review for gene: CELF4 was set to GREEN
Added comment: 15 individuals with de novo missense variants clustering in the N-terminal reported, LoF is the likely mechanism. Most individuals presented with neurodevelopmental disorders including global developmental delay/intellectual disability (11/14), seizures (9/15) and overweight/obesity (10/14). Clinical features are similar to the reported celf4-mouse mutant phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.94 CELF4 Zornitza Stark Marked gene: CELF4 as ready
Intellectual disability syndromic and non-syndromic v1.94 CELF4 Zornitza Stark Gene: celf4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.94 CELF4 Zornitza Stark Classified gene: CELF4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.94 CELF4 Zornitza Stark Gene: celf4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.93 CELF4 Zornitza Stark gene: CELF4 was added
gene: CELF4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CELF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELF4 were set to 40108438
Phenotypes for gene: CELF4 were set to Neurodevelopmental disorder, MONDO:0700092, CELF4-related
Review for gene: CELF4 was set to GREEN
Added comment: 15 individuals with de novo missense variants clustering in the N-terminal reported, LoF is the likely mechanism. Most individuals presented with neurodevelopmental disorders including global developmental delay/intellectual disability (11/14), seizures (9/15) and overweight/obesity (10/14). Clinical features are similar to the reported celf4-mouse mutant phenotype.
Sources: Literature
Mendeliome v1.2404 CSNK1A1 Zornitza Stark Marked gene: CSNK1A1 as ready
Mendeliome v1.2404 CSNK1A1 Zornitza Stark Gene: csnk1a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2404 CSNK1A1 Zornitza Stark Classified gene: CSNK1A1 as Amber List (moderate evidence)
Mendeliome v1.2404 CSNK1A1 Zornitza Stark Gene: csnk1a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2403 CSNK1A1 Zornitza Stark gene: CSNK1A1 was added
gene: CSNK1A1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CSNK1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK1A1 were set to 40156289
Phenotypes for gene: CSNK1A1 were set to Infantile spasms, MONDO:0018097, CSNK1A1-related
Review for gene: CSNK1A1 was set to AMBER
Added comment: Two individuals with de novo variants and some supportive functional data.
Sources: Literature
Genetic Epilepsy v1.122 CSNK1A1 Zornitza Stark Marked gene: CSNK1A1 as ready
Genetic Epilepsy v1.122 CSNK1A1 Zornitza Stark Gene: csnk1a1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.122 CSNK1A1 Zornitza Stark Classified gene: CSNK1A1 as Amber List (moderate evidence)
Genetic Epilepsy v1.122 CSNK1A1 Zornitza Stark Gene: csnk1a1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.121 CSNK1A1 Zornitza Stark gene: CSNK1A1 was added
gene: CSNK1A1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: CSNK1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK1A1 were set to 40156289
Phenotypes for gene: CSNK1A1 were set to Infantile spasms, MONDO:0018097, CSNK1A1-related
Review for gene: CSNK1A1 was set to AMBER
Added comment: Two individuals with de novo variants and some supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.92 SVBP Zornitza Stark Phenotypes for gene: SVBP were changed from Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly; OMIM #618569 to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, MIM #618569; Spastic paraplegia 94, autosomal recessive, MIM# 621150
Intellectual disability syndromic and non-syndromic v1.91 SVBP Zornitza Stark Publications for gene: SVBP were set to PMID: 31363758; 30607023
Intellectual disability syndromic and non-syndromic v1.90 SVBP Zornitza Stark edited their review of gene: SVBP: Added comment: PMID 39412222: 6 individuals from 3 families with spastic paraplegia and the same homozygous missense (L49P). Presented from birth or childhood with DD/ID and spastic paraplegia. Additional features: verbal apraxia, axonal neuropathy, ataxia, nystagmus, epilepsy, and aggressive behaviour. Brain MRIs were performed in 3 individuals and showed thinning of the corpus callosum, cerebellar atrophy, and ventriculomegaly; frontal ventricular hyperintensities suggestive of the 'ear of the lynx' sign in 2. Three individuals had a history of cancer of epithelial origin, including adenocarcinoma (patient 1), colonic tubular adenoma (patient 2), and breast cancer (patient 3).; Changed publications: 39412222; Changed phenotypes: Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, MIM #618569, Spastic paraplegia 94, autosomal recessive, MIM# 621150
Mendeliome v1.2402 SVBP Zornitza Stark Phenotypes for gene: SVBP were changed from Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly; OMIM #618569 to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, MIM #618569; Spastic paraplegia 94, autosomal recessive, MIM# 621150
Mendeliome v1.2401 SVBP Zornitza Stark Publications for gene: SVBP were set to 31363758; 30607023
Mendeliome v1.2400 SVBP Zornitza Stark edited their review of gene: SVBP: Added comment: PMID 39412222: 6 individuals from 3 families with spastic paraplegia and the same homozygous missense (L49P). Presented from birth or childhood with DD/ID and spastic paraplegia. Additional features: verbal apraxia, axonal neuropathy, ataxia, nystagmus, epilepsy, and aggressive behaviour. Brain MRIs were performed in 3 individuals and showed thinning of the corpus callosum, cerebellar atrophy, and ventriculomegaly; frontal ventricular hyperintensities suggestive of the 'ear of the lynx' sign in 2. Three individuals had a history of cancer of epithelial origin, including adenocarcinoma (patient 1), colonic tubular adenoma (patient 2), and breast cancer (patient 3).; Changed publications: 31363758, 30607023, 39412222; Changed phenotypes: Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, MIM #618569, Spastic paraplegia 94, autosomal recessive, MIM# 621150
Hereditary Spastic Paraplegia - paediatric v1.89 SVBP Zornitza Stark Marked gene: SVBP as ready
Hereditary Spastic Paraplegia - paediatric v1.89 SVBP Zornitza Stark Gene: svbp has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - paediatric v1.89 SVBP Zornitza Stark Classified gene: SVBP as Amber List (moderate evidence)
Hereditary Spastic Paraplegia - paediatric v1.89 SVBP Zornitza Stark Gene: svbp has been classified as Amber List (Moderate Evidence).
Hereditary Spastic Paraplegia - paediatric v1.88 SVBP Zornitza Stark gene: SVBP was added
gene: SVBP was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
founder tags were added to gene: SVBP.
Mode of inheritance for gene: SVBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SVBP were set to 39412222
Phenotypes for gene: SVBP were set to Spastic paraplegia 94, autosomal recessive, MIM# 621150
Review for gene: SVBP was set to AMBER
Added comment: 6 individuals from 3 families with spastic paraplegia and the same homozygous missense (L49P). Presented from birth or childhood with DD/ID and spastic paraplegia. Additional features: verbal apraxia, axonal neuropathy, ataxia, nystagmus, epilepsy, and aggressive behaviour. Brain MRIs were performed in 3 individuals and showed thinning of the corpus callosum, cerebellar atrophy, and ventriculomegaly; frontal ventricular hyperintensities suggestive of the 'ear of the lynx' sign in 2. Three individuals had a history of cancer of epithelial origin, including adenocarcinoma (patient 1), colonic tubular adenoma (patient 2), and breast cancer (patient 3).
Sources: Literature
Mendeliome v1.2400 CFAP54 Achchuthan Shanmugasundram reviewed gene: CFAP54: Rating: GREEN; Mode of pathogenicity: None; Publications: 39362668; Phenotypes: Ciliary dyskinesia, primary, 54, OMIM:621125; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arrhythmogenic Cardiomyopathy v0.68 TAX1BP3 Ivan Macciocca gene: TAX1BP3 was added
gene: TAX1BP3 was added to Arrhythmogenic Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: TAX1BP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAX1BP3 were set to (PMID: 39963794)
Phenotypes for gene: TAX1BP3 were set to arrhythmogenic cardiomyopathy
Penetrance for gene: TAX1BP3 were set to unknown
Review for gene: TAX1BP3 was set to AMBER
Added comment: Biallelic variants (1 x del, 1 x missense) in TAX1BP3 cause a novel autosomal recessive form of arrhythmogenic cardiomyopathy.
One family only, but 3 affected sibs had the bialleic variants which were absent in an unaffected sister. Carrier parents were normal.
Experimental work on patient-derived induced pluripotent stem cell cardiac myocytes and a knockout mouse showed that show loss of TAX1BP3 causes calcium dysregulation in cardiomyocytes, a known mechanism for arrhythmia.

Suggest this one is AMBER until more case level data evolves.
Sources: Literature
Mendeliome v1.2400 NR2F2 Elena Savva Phenotypes for gene: NR2F2 were changed from 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 Current 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 Edit; 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 to Syndromic disease, MONDO:0002254, NR2F2-related
Mendeliome v1.2399 NR2F2 Elena Savva Phenotypes for gene: NR2F2 were changed from Krithika Murali (Victorian Clinical Genetics Services) 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 Current 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 Edit; 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 to 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 Current 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779 Edit; 46,XX sex reversal 5 - MIM#618901; Congenital heart defects, multiple types, 4 - MIM#615779
Mendeliome v1.2398 CFAP74 Achchuthan Shanmugasundram reviewed gene: CFAP74: Rating: GREEN; Mode of pathogenicity: None; Publications: 32555313, 36047773, 39362668; Phenotypes: Ciliary dyskinesia, primary, 49, without situs inversus, OMIM:620197; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2398 NEB Sangavi Sivagnanasundram reviewed gene: NEB: Rating: AMBER; Mode of pathogenicity: None; Publications: 39802796, 30679003, 33933294; Phenotypes: congenital structural myopathy MONDO:0002921; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.2398 FAM126A Sangavi Sivagnanasundram commented on gene: FAM126A
Combined Immunodeficiency v1.115 TFRC Sangavi Sivagnanasundram reviewed gene: TFRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 32851577, 38270687; Phenotypes: TFRC-related combined immunodeficiency MONDO:0014760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2398 TFRC Sangavi Sivagnanasundram reviewed gene: TFRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 32851577, 38270687; Phenotypes: TFRC-related combined immunodeficiency MONDO:0014760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.90 CRMP1 Zornitza Stark Marked gene: CRMP1 as ready
Intellectual disability syndromic and non-syndromic v1.90 CRMP1 Zornitza Stark Gene: crmp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.90 CRMP1 Zornitza Stark Classified gene: CRMP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.90 CRMP1 Zornitza Stark Gene: crmp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.89 CRMP1 Zornitza Stark gene: CRMP1 was added
gene: CRMP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: CRMP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRMP1 were set to 36511780; 39758889
Phenotypes for gene: CRMP1 were set to neurodevelopmental disorder, MONDO:0700092, CRMP2-related
Review for gene: CRMP1 was set to GREEN
Added comment: PMID:36511780 reported the identification of three different heterozygous de novo variants in the CRMP1 gene (p.(Pro589Leu), p.(Thr427Met) & p.(Phe351Ser)) in three unrelated individuals with a neurodevelopmental disorder presenting with muscular hypotonia, intellectual disability, and/or autism spectrum disorder. ID was moderate in two of them, while IQ was normal in one. There is also functional evidence available for these variants.

PMID:39758889 reported the identification of a novel heterozygous de novo frameshift variant in CRMP1 (p.(Lys586fs)) in a 9-year-old male patient presenting with phenotypes such as autism, language delay, hyperactivity, and learning disabilities. This patient was reported with moderate ID.

Four individuals with neurodevelopmental disorders and de novo variants in this gene.
Sources: Expert Review
Mendeliome v1.2398 CRMP1 Zornitza Stark Marked gene: CRMP1 as ready
Mendeliome v1.2398 CRMP1 Zornitza Stark Gene: crmp1 has been classified as Green List (High Evidence).
Mendeliome v1.2398 CRMP1 Zornitza Stark Phenotypes for gene: CRMP1 were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092, CRMP2-related
Mendeliome v1.2397 CRMP1 Zornitza Stark Classified gene: CRMP1 as Green List (high evidence)
Mendeliome v1.2397 CRMP1 Zornitza Stark Gene: crmp1 has been classified as Green List (High Evidence).
Mendeliome v1.2396 CRMP1 Zornitza Stark reviewed gene: CRMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder, MONDO:0700092, CRMP2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Metal Metabolism Disorders v0.48 HEPHL1 Zornitza Stark Classified gene: HEPHL1 as Red List (low evidence)
Metal Metabolism Disorders v0.48 HEPHL1 Zornitza Stark Gene: hephl1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.1818 PDHX Zornitza Stark Marked gene: PDHX as ready
Prepair 1000+ v1.1818 PDHX Zornitza Stark Added comment: Comment when marking as ready: Meets criteria, for inclusion in next version.
Prepair 1000+ v1.1818 PDHX Zornitza Stark Gene: pdhx has been removed from the panel.
Prepair 1000+ v1.1818 PDHX Zornitza Stark Tag for review tag was added to gene: PDHX.
Prepair 1000+ v1.1818 OTULIN Zornitza Stark Marked gene: OTULIN as ready
Prepair 1000+ v1.1818 OTULIN Zornitza Stark Added comment: Comment when marking as ready: For review. Likely meets criteria for inclusion in next version.
Prepair 1000+ v1.1818 OTULIN Zornitza Stark Gene: otulin has been removed from the panel.
Prepair 1000+ v1.1818 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from to Autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive MIM#617099
Prepair 1000+ v1.1817 OTULIN Zornitza Stark Publications for gene: OTULIN were set to
Prepair 1000+ v1.1816 OTULIN Zornitza Stark Tag for review tag was added to gene: OTULIN.
Prepair 1000+ v1.1816 AGTR1 Zornitza Stark Marked gene: AGTR1 as ready
Prepair 1000+ v1.1816 AGTR1 Zornitza Stark Added comment: Comment when marking as ready: Meets criteria, for inclusion in next version.
Prepair 1000+ v1.1816 AGTR1 Zornitza Stark Gene: agtr1 has been removed from the panel.
Prepair 1000+ v1.1816 AGTR1 Zornitza Stark Tag for review tag was added to gene: AGTR1.
Prepair 1000+ v1.1816 MTPAP Zornitza Stark Marked gene: MTPAP as ready
Prepair 1000+ v1.1816 MTPAP Zornitza Stark Added comment: Comment when marking as ready: Meets criteria, for inclusion in next version.
Prepair 1000+ v1.1816 MTPAP Zornitza Stark Gene: mtpap has been removed from the panel.
Prepair 1000+ v1.1816 MTPAP Zornitza Stark Tag for review tag was added to gene: MTPAP.
Prepair 1000+ v1.1816 RBM8A Zornitza Stark Marked gene: RBM8A as ready
Prepair 1000+ v1.1816 RBM8A Zornitza Stark Gene: rbm8a has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.1816 RBM8A Zornitza Stark Classified gene: RBM8A as Amber List (moderate evidence)
Prepair 1000+ v1.1816 RBM8A Zornitza Stark Gene: rbm8a has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.1815 RBM8A Zornitza Stark reviewed gene: RBM8A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombocytopenia-absent radius syndrome MIM#274000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1815 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Prepair 1000+ v1.1815 SCO1 Zornitza Stark Added comment: Comment when marking as ready: Meets criteria, for inclusion in next version.
Prepair 1000+ v1.1815 SCO1 Zornitza Stark Gene: sco1 has been removed from the panel.
Prepair 1000+ v1.1815 SCO1 Zornitza Stark Tag for review tag was added to gene: SCO1.
Prepair 1000+ v1.1815 PEX19 Zornitza Stark Marked gene: PEX19 as ready
Prepair 1000+ v1.1815 PEX19 Zornitza Stark Added comment: Comment when marking as ready: Meets criteria, for inclusion in next version.
Prepair 1000+ v1.1815 PEX19 Zornitza Stark Gene: pex19 has been removed from the panel.
Prepair 1000+ v1.1815 PEX19 Zornitza Stark Tag for review tag was added to gene: PEX19.
Prepair 1000+ v1.1815 BRWD3 Zornitza Stark Marked gene: BRWD3 as ready
Prepair 1000+ v1.1815 BRWD3 Zornitza Stark Gene: brwd3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1815 BRWD3 Zornitza Stark Phenotypes for gene: BRWD3 were changed from Mental retardation, X-linked 93, 300659 (3) to Intellectual developmental disorder, X-linked 93 MIM#300659
Prepair 1000+ v1.1814 BRWD3 Zornitza Stark Publications for gene: BRWD3 were set to
Prepair 1000+ v1.1813 CASK Zornitza Stark Marked gene: CASK as ready
Prepair 1000+ v1.1813 CASK Zornitza Stark Gene: cask has been classified as Green List (High Evidence).
Prepair 1000+ v1.1813 CASK Zornitza Stark Phenotypes for gene: CASK were changed from Mental retardation, with or without nystagmus to X-linked syndromic intellectual disability MONDO:0020119
Prepair 1000+ v1.1812 CASK Zornitza Stark Publications for gene: CASK were set to
Mendeliome v1.2396 PIGQ Sangavi Sivagnanasundram reviewed gene: PIGQ: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008756; Phenotypes: developmental and epileptic encephalopathy, 77 MONDO:0032808; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Metal Metabolism Disorders v0.47 HEPHL1 Sangavi Sivagnanasundram gene: HEPHL1 was added
gene: HEPHL1 was added to Metal Metabolism Disorders. Sources: ClinGen
Mode of inheritance for gene: HEPHL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEPHL1 were set to 31125343
Phenotypes for gene: HEPHL1 were set to pili torti-developmental delay-neurological abnormalities syndrome MONDO:0009871
Review for gene: HEPHL1 was set to RED
Added comment: Classified as LIMITED by General Inborn Errors of Metabolism GCEP on 28/03/2025 - https://search.clinicalgenome.org/CCID:008755

Reported in a proband with biallelic variant. The variant was shown to affect ferroxidase activity result in abnormal hair phenotype. ?inborn error of iron metabolism
Sources: ClinGen
Mendeliome v1.2396 HEPHL1 Sangavi Sivagnanasundram changed review comment from: Classified as LIMITED by General Inborn Errors of Metabolism GCEP on 28/03/2025 - https://search.clinicalgenome.org/CCID:008755

Reported in a proband with chet variant. The variant was shown to affect ferroxidase activity result in abnormal hair phenotype. ?inborn error of iron metabolism; to: Classified as LIMITED by General Inborn Errors of Metabolism GCEP on 28/03/2025 - https://search.clinicalgenome.org/CCID:008755

Reported in a proband with biallelic variant. The variant was shown to affect ferroxidase activity result in abnormal hair phenotype. ?inborn error of iron metabolism
Mendeliome v1.2396 HEPHL1 Sangavi Sivagnanasundram changed review comment from: Classified as LIMITED by General Inborn Errors of Metabolism GCEP on 28/03/2025 - https://search.clinicalgenome.org/CCID:008755

Reported in a proband with chet variants. The variant was shown to affect ferroxidase activity result in abnormal hair phenotype. ?inborn error of iron metabolism; to: Classified as LIMITED by General Inborn Errors of Metabolism GCEP on 28/03/2025 - https://search.clinicalgenome.org/CCID:008755

Reported in a proband with chet variant. The variant was shown to affect ferroxidase activity result in abnormal hair phenotype. ?inborn error of iron metabolism
Mendeliome v1.2396 HEPHL1 Sangavi Sivagnanasundram reviewed gene: HEPHL1: Rating: RED; Mode of pathogenicity: None; Publications: 31125343; Phenotypes: pili torti-developmental delay-neurological abnormalities syndrome MONDO:0009871; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2396 MAN2B2 Zornitza Stark Phenotypes for gene: MAN2B2 were changed from Congenital disorder of glycosylation, MONDO:0015286, MAN2B2-related; immunodeficiency to Congenital disorder of glycosylation type 1EE with or without immunodeficiency, MIM# 621140
Mendeliome v1.2395 MAN2B2 Zornitza Stark Classified gene: MAN2B2 as Green List (high evidence)
Mendeliome v1.2395 MAN2B2 Zornitza Stark Gene: man2b2 has been classified as Green List (High Evidence).
Mendeliome v1.2394 MAN2B2 Zornitza Stark edited their review of gene: MAN2B2: Added comment: Third individual reported PMID 38622837 with compound het missense variants, supportive functional data.; Changed rating: GREEN; Changed publications: 31775018, 35637269, 38622837; Changed phenotypes: Congenital disorder of glycosylation type 1EE with or without immunodeficiency, MIM# 621140
Congenital Disorders of Glycosylation v1.62 MAN2B2 Zornitza Stark Phenotypes for gene: MAN2B2 were changed from Congenital disorder of glycosylation, MONDO:0015286, MAN2B2-related to Congenital disorder of glycosylation type 1EE with or without immunodeficiency, MIM# 621140
Congenital Disorders of Glycosylation v1.61 MAN2B2 Zornitza Stark Classified gene: MAN2B2 as Green List (high evidence)
Congenital Disorders of Glycosylation v1.61 MAN2B2 Zornitza Stark Gene: man2b2 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v1.61 MAN2B2 Zornitza Stark Classified gene: MAN2B2 as Green List (high evidence)
Congenital Disorders of Glycosylation v1.61 MAN2B2 Zornitza Stark Gene: man2b2 has been classified as Green List (High Evidence).
Congenital Disorders of Glycosylation v1.60 MAN2B2 Zornitza Stark edited their review of gene: MAN2B2: Added comment: Third individual reported PMID 38622837 with compound het missense variants, supportive functional data.; Changed rating: GREEN; Changed publications: 31775018, 35637269, 38622837; Changed phenotypes: Congenital disorder of glycosylation type 1EE with or without immunodeficiency, MIM# 621140
Progressive Neurological Conditions v19.84 Zornitza Stark Panel types changed to Superpanel; Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Prepair 1000+ v1.1811 CASK Andrew Coventry reviewed gene: CASK: Rating: GREEN; Mode of pathogenicity: None; Publications: 21954287, 12522552, 19377476, 20029458, 28139025, 28944139; Phenotypes: X-linked syndromic intellectual disability MONDO:0020119; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.1811 BRWD3 Andrew Coventry reviewed gene: BRWD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 17668385, 30628072, 24462886; Phenotypes: Intellectual developmental disorder, X-linked 93 MIM#300659; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.2394 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome, MIM# 236700; Retinitis pigmentosa to Ciliopathy, MONDO:0005308, MKKS-related; Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome, MIM# 236700; Retinitis pigmentosa
Ciliopathies v1.63 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome, MIM# 236700; Retinitis pigmentosa to Ciliopathy, MONDO:0005308, MKKS-related; Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome, MIM# 236700; Retinitis pigmentosa
Ciliopathies v1.62 MKKS Zornitza Stark edited their review of gene: MKKS: Changed phenotypes: Ciliopathy, MONDO:0005308, MKKS-related, McKusick-Kaufman syndrome, MIM# 236700, Retinitis pigmentosa.
Deafness_Isolated v1.69 MEPE Zornitza Stark Marked gene: MEPE as ready
Deafness_Isolated v1.69 MEPE Zornitza Stark Gene: mepe has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.69 MEPE Zornitza Stark Classified gene: MEPE as Amber List (moderate evidence)
Deafness_Isolated v1.69 MEPE Zornitza Stark Gene: mepe has been classified as Amber List (Moderate Evidence).
Deafness_Isolated v1.68 MEPE Zornitza Stark gene: MEPE was added
gene: MEPE was added to Deafness_Isolated. Sources: Expert Review
Mode of inheritance for gene: MEPE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEPE were set to 30287925
Phenotypes for gene: MEPE were set to Nonsyndromic genetic hearing loss, MONDO:0019497, MEPE-related; hereditary congenital facial paresis; otosclerosis
Review for gene: MEPE was set to AMBER
Added comment: Single four-generation family reported with variant in this gene segregating nonprogressive HCFP and mixed hearing loss (HL). Damaging variants (truncating/frameshift) found to be enriched in otosclerosis cohort (p = 0.0006–0.0060).
Sources: Expert Review
Mendeliome v1.2393 MEPE Zornitza Stark Phenotypes for gene: MEPE were changed from hereditary congenital facial paresis; otosclerosis to Nonsyndromic genetic hearing loss, MONDO:0019497, MEPE-related; hereditary congenital facial paresis; otosclerosis
Mendeliome v1.2392 MEPE Zornitza Stark edited their review of gene: MEPE: Changed phenotypes: Nonsyndromic genetic hearing loss, MONDO:0019497, MEPE-related, hereditary congenital facial paresis, otosclerosis
Lipodystrophy_Lipoatrophy v1.20 MCM7 Zornitza Stark Phenotypes for gene: MCM7 were changed from Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency to Syndromic disease, MONDO:0002254, MCM7-related; Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency
Fetal anomalies v1.318 MCM7 Zornitza Stark Phenotypes for gene: MCM7 were changed from Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency to Syndromic disease, MONDO:0002254, MCM7-related; Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency
Microcephaly v1.302 MCM7 Zornitza Stark Phenotypes for gene: MCM7 were changed from Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency to Syndromic disease, MONDO:0002254, MCM7-related; Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency
Microcephaly v1.301 MCM7 Zornitza Stark edited their review of gene: MCM7: Changed phenotypes: Syndromic disease, MONDO:0002254, MCM7-related, Meier-Gorlin syndrome, Microcephaly, Intellectual disability, Lipodystrophy, Adrenal insufficiency
Mendeliome v1.2392 MCM7 Zornitza Stark Phenotypes for gene: MCM7 were changed from Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency to Syndromic disease, MONDO:0002254, MCM7-related; Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency
Mendeliome v1.2391 MCM7 Zornitza Stark reviewed gene: MCM7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic disease, MONDO:0002254, MCM7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2391 MACROD2 Zornitza Stark Phenotypes for gene: MACROD2 were changed from intellectual disability; dysmorphic features; microcephaly to Syndromic disease, MONDO:0002254, MACROD2-related; intellectual disability; dysmorphic features; microcephaly
Mendeliome v1.2390 MACROD2 Zornitza Stark edited their review of gene: MACROD2: Changed phenotypes: Syndromic disease, MONDO:0002254, MACROD2-related, intellectual disability, dysmorphic features, microcephaly
Intellectual disability syndromic and non-syndromic v1.88 MACROD2 Zornitza Stark Phenotypes for gene: MACROD2 were changed from Syndromic disease, MONDO:0002254, MACROD2-related to Syndromic disease, MONDO:0002254, MACROD2-related
Intellectual disability syndromic and non-syndromic v1.88 MACROD2 Zornitza Stark Phenotypes for gene: MACROD2 were changed from no OMIM number yet to Syndromic disease, MONDO:0002254, MACROD2-related
Prepair 1000+ v1.1811 PEX19 Andrew Coventry gene: PEX19 was added
gene: PEX19 was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: PEX19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX19 were set to 10051604; 20683989; 39757991; 21031596; 30561787; 36931687
Phenotypes for gene: PEX19 were set to Peroxisome biogenesis disorder 12A (Zellweger) MIM#614886; Peroxisome biogenesis disorder MONDO:0019234
Review for gene: PEX19 was set to GREEN
Added comment: Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life.

Functional studies and animal models are present.
Reported in individuals across at least 4 unrelated families.
Sources: Literature
Prepair 1000+ v1.1811 SCO1 Andrew Coventry changed review comment from: Four unrelated families reported, typically presenting with lactatic acidosis and encephalopathy in infancy. SCO1 pathogenic variants were first described in an infant with respiratory distress, metabolic acidosis, hepatic failure, and encephalopathy in the setting of profound complex IV deficiency in muscle and liver. Further reports have shown phenotypic spectrum to include cardiomyopathy, encephalopathy, and lactic acidosis without cardiac or hepatic involvement. Many cases are fatal in the first few months of life.
Functional studies and model organisms also present.

ClinGen: While various names have been given to the constellation of features seen in those with SCO1-related disease, pathogenic variants in this gene cause a primary mitochondrial disease. Therefore, the SCO1 phenotype has been lumped into one disease entity.
Sources: Literature; to: Six unrelated families reported.
Typically presenting with lactatic acidosis and encephalopathy in infancy. SCO1 pathogenic variants were first described in an infant with respiratory distress, metabolic acidosis, hepatic failure, and encephalopathy in the setting of profound complex IV deficiency in muscle and liver. Further reports have shown phenotypic spectrum to include cardiomyopathy, encephalopathy, and lactic acidosis without cardiac or hepatic involvement. Many cases are fatal in the first few months of life.
Functional studies and model organisms also present.

ClinGen: While various names have been given to the constellation of features seen in those with SCO1-related disease, pathogenic variants in this gene cause a primary mitochondrial disease. Therefore, the SCO1 phenotype has been lumped into one disease entity.

PMID: 39214134: 3 cases from 2 unrelated families, with developmental and epileptic encephalopathy, hypopituitarism.
Prepair 1000+ v1.1811 SCO1 Andrew Coventry gene: SCO1 was added
gene: SCO1 was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: SCO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCO1 were set to 11013136; 19295170; 31352446; 23878101
Phenotypes for gene: SCO1 were set to Mitochondrial disease MONDO:0044970; Mitochondrial complex IV deficiency, nuclear type 4 MIM#619048
Review for gene: SCO1 was set to GREEN
Added comment: Four unrelated families reported, typically presenting with lactatic acidosis and encephalopathy in infancy. SCO1 pathogenic variants were first described in an infant with respiratory distress, metabolic acidosis, hepatic failure, and encephalopathy in the setting of profound complex IV deficiency in muscle and liver. Further reports have shown phenotypic spectrum to include cardiomyopathy, encephalopathy, and lactic acidosis without cardiac or hepatic involvement. Many cases are fatal in the first few months of life.
Functional studies and model organisms also present.

ClinGen: While various names have been given to the constellation of features seen in those with SCO1-related disease, pathogenic variants in this gene cause a primary mitochondrial disease. Therefore, the SCO1 phenotype has been lumped into one disease entity.
Sources: Literature
Prepair 1000+ v1.1811 RBM8A Andrew Coventry gene: RBM8A was added
gene: RBM8A was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: RBM8A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBM8A were set to 22366785; 17236129; 26550033; 32227665
Phenotypes for gene: RBM8A were set to Thrombocytopenia-absent radius syndrome MIM#274000
Review for gene: RBM8A was set to AMBER
Added comment: The thrombocytopenia-absent radius syndrome (TAR) is characterised by reduction in the number of platelets and absence of the radius; preservation of the thumb distinguishes TAR from other syndromes that combine blood abnormalities with absence of the radius, such as Fanconi anemia. Individuals with TAR have low numbers of megakaryocytes, platelet precursor cells that reside in bone marrow, and frequently present with bleeding episodes in the first year of life that diminish in frequency and severity with age. The severity of skeletal anomalies varies from absence of radii to virtual absence of upper limbs, with or without lower limb defects such as malformations of the hip and knee.

Vast majority of cases include a recurrent 200kb deletion on one allele (although truncations are seen) and the presence of 1 of 2 SNPs in trans. The SNPs have a MAF of 3.05% and 0.42%. Cases have been reported with this phenotype without the 200kb deletion (PMID: 22366785, 32227665).

Currently, the large CNV in majority of cases would not be detected.
Sources: Literature
Prepair 1000+ v1.1811 MTPAP Andrew Coventry gene: MTPAP was added
gene: MTPAP was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: MTPAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTPAP were set to 20970105; 33340416; 32376682; 15769737; 31779033; 35235001; 27391121
Phenotypes for gene: MTPAP were set to Mitochondrial disease MONDO:0044970
Review for gene: MTPAP was set to GREEN
Added comment: Definitive disease-gene classification by ClinGen - "Identified in five individuals from four publications (PMIDs: 20970105, 31779033, 35235001, 27391121). Supported by a biochemical function (mitochondrial translation) shared with other genes associated with primary mitochondrial disease, early embryonic lethality and failure of developmental progression in a knockout mouse model, and disrupted expression of mitochondrial proteins and mitochondrial dysfunction following gene knockdown in HeLa cells (PMIDs: 33340416, 32376682, 15769737)."

Note that 6 individuals with spastic ataxia all had same founder variant and were traced as distantly related (Amish community - c.1432A>G (p.Asn478Asp).
Further additional families reported with a much more severe phenotype of lethal encephalopathy.

Phenotypes previous reported to be associated with MTPAP are likely to represent a continuum of severity associated with a mitochondrial disorder.
Clingen "While various names have been given to the constellation of features seen in those with MTPAP-related disease, including autosomal recessive spastic ataxia 4 (SPAX4) (MIM 613672) in additional to other mitochondrial disorders, pathogenic variants in this gene cause a primary mitochondrial disease.... lumped into one disease entity..."
Sources: Literature
Prepair 1000+ v1.1811 AGTR1 Andrew Coventry gene: AGTR1 was added
gene: AGTR1 was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: AGTR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGTR1 were set to 16116425; 22095942
Phenotypes for gene: AGTR1 were set to Renal tubular dysgenesis MIM#267430
Review for gene: AGTR1 was set to GREEN
Added comment: Severe disorder of renal tubular development characterised by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Can cause stillbirth. Three unrelated families reported for AGTR1 variants.
Other genes associated with this phenotype are included in 1000+.
Sources: Literature
Prepair 1000+ v1.1811 OTULIN Andrew Coventry reviewed gene: OTULIN: Rating: AMBER; Mode of pathogenicity: None; Publications: 27523608, 27559085, 30796585, 35170849; Phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, autosomal recessive MIM#617099; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1811 PDHX Andrew Coventry gene: PDHX was added
gene: PDHX was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: PDHX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDHX were set to 20002125; 34873726; 33092611; 30981218; 25087164; 22766002; 12557299; 14518830; 15303005; 16566017; 27343776
Phenotypes for gene: PDHX were set to Lacticacidemia due to PDX1 deficiency MIM#245349; Mitochondrial disease MONDO:0044970
Review for gene: PDHX was set to GREEN
Added comment: Established gene-disease association.
Clingen definitive for mitochondrial disease: "While various names have been given to the constellation of features seen in those with PDHX-related disorders, including pyruvate dehydrogenase complex deficiency or PDCD, pathogenic variants in this gene ultimately cause a primary mitochondrial disease. Therefore, the PDHX phenotype has been lumped into one disease entity according to the ClinGen Lumping and Splitting Framework."

Condition is a metabolic disorder associated with abnormal function of the mitochondria in cells, thus depriving the body of energy. Progressive neurological symptoms usually start in infancy but may be evident at birth, or in later childhood; these symptoms may include developmental delay, intermittent ataxia, poor muscle tone (hypotonia), abnormal eye movements, or seizures. Severe lethargy, poor feeding, and tachypnea (rapid breathing) commonly occur, especially during times of illness, stress, or high carbohydrate intake.

Clingen: Age of onset ranges from the first days of life to later in childhood, with some individuals living well into adulthood. Clinical features in affected individuals include neonatal lactic acidosis, LSS, seizures, spasticity, agenesis of the corpus callosum, cerebral atrophy, vomiting, and optic atrophy.

Note:
PDHX c.1336C>T (p.Arg446Ter) is a Roma founder variant;
c.1182+2T>C (p.Ile386SerfsTer13) is a Moroccan founder variant.
Sources: Literature
Intellectual disability syndromic and non-syndromic v1.87 SLC35F1 Zornitza Stark Phenotypes for gene: SLC35F1 were changed from Neruodevelopmental disorder, MONDO:0700092, SLC35F1-associated; Rett-like syndrome to Neurodevelopmental disorder, MONDO:0700092, SLC35F1-associated; Rett-like syndrome
Intellectual disability syndromic and non-syndromic v1.86 SLC35F1 Zornitza Stark edited their review of gene: SLC35F1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SLC35F1-associated, Rett-like syndrome
Mendeliome v1.2390 SLC35F1 Zornitza Stark Phenotypes for gene: SLC35F1 were changed from Neruodevelopmental disorder, MONDO:0700092, SLC35F1-associated; Rett-like syndrome to Neurodevelopmental disorder, MONDO:0700092, SLC35F1-associated; Rett-like syndrome
Mendeliome v1.2389 SIX5 Zornitza Stark Classified gene: SIX5 as Red List (low evidence)
Mendeliome v1.2389 SIX5 Zornitza Stark Gene: six5 has been classified as Red List (Low Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.146 SIX5 Zornitza Stark Classified gene: SIX5 as Red List (low evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.146 SIX5 Zornitza Stark Gene: six5 has been classified as Red List (Low Evidence).
Fetal anomalies v1.317 SLC30A5 Zornitza Stark Phenotypes for gene: SLC30A5 were changed from Perinatal lethal cardiomyopathy to Cardiomyopathy MONDO:0004994, SLC30A5-related; Perinatal lethal cardiomyopathy
Cardiomyopathy_Paediatric v0.197 SLC30A5 Zornitza Stark Phenotypes for gene: SLC30A5 were changed from Perinatal lethal cardiomyopathy to Cardiomyopathy MONDO:0004994, SLC30A5-related; Perinatal lethal cardiomyopathy
Mendeliome v1.2388 SLC30A5 Zornitza Stark Phenotypes for gene: SLC30A5 were changed from Perinatal lethal cardiomyopathy to Cardiomyopathy MONDO:0004994, SLC30A5-related; Perinatal lethal cardiomyopathy
Hydrops fetalis v0.325 SLC30A5 Zornitza Stark Phenotypes for gene: SLC30A5 were changed from Perinatal lethal cardiomyopathy to Cardiomyopathy MONDO:0004994, SLC30A5-related; Perinatal lethal cardiomyopathy
Mendeliome v1.2387 SLC2A1 Zornitza Stark Phenotypes for gene: SLC2A1 were changed from GLUT1 deficiency syndrome 1, infantile onset, severe, MIM#606777; Dystonia 9, MIM#601042; Stomatin-deficient cryohydrocytosis with neurologic defects, MIM#608885; GLUT1 deficiency syndrome 2, childhood onset, MIM#612126; {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM#614847 to GLUT1 deficiency syndrome, MONDO:0000188; GLUT1 deficiency syndrome 1, infantile onset, severe, MIM#606777; Dystonia 9, MIM#601042; Stomatin-deficient cryohydrocytosis with neurologic defects, MIM#608885; GLUT1 deficiency syndrome 2, childhood onset, MIM#612126; {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM#614847
Mendeliome v1.2386 RALGAPB Lucy Spencer reviewed gene: RALGAPB: Rating: RED; Mode of pathogenicity: None; Publications: 35830182; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), RALGAPB-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2386 CRMP1 Achchuthan Shanmugasundram changed review comment from: PMID:36511780 reported the identification of three different heterozygous de novo variants in the CRMP1 gene (p.(Pro589Leu), p.(Thr427Met) & p.(Phe351Ser)) in three unrelated individuals with a neurodevelopmental disorder presenting with muscular hypotonia, intellectual disability, and/or autism spectrum disorder. ID was moderate in two of them, while IQ was normal in one. There is also functional evidence available for these variants.

PMID:39758889 reported the identification of a novel heterozygous de novo frameshift variant in CRMP1 (p.(Lys586fs)) in a 9-year-old male patient presenting with phenotypes such as autism, language delay, hyperactivity, and learning disabilities. This patient was reported with moderate ID.

There are three unrelated cases reported with moderate intellectual disability and with monoallelic CRMP1 variants. However, one patient with a different monoallelic CRMP1 variant had normal IQ. Hence, this gene should be rated amber with current evidence.
Sources: Literature; to: PMID:36511780 reported the identification of three different heterozygous de novo variants in the CRMP1 gene (p.(Pro589Leu), p.(Thr427Met) & p.(Phe351Ser)) in three unrelated individuals with a neurodevelopmental disorder presenting with muscular hypotonia, intellectual disability, and/or autism spectrum disorder. ID was moderate in two of them, while IQ was normal in one. There is also functional evidence available for these variants.

PMID:39758889 reported the identification of a novel heterozygous de novo frameshift variant in CRMP1 (p.(Lys586fs)) in a 9-year-old male patient presenting with phenotypes such as autism, language delay, hyperactivity, and learning disabilities. This patient was reported with moderate ID.

Summary: There are three unrelated cases reported with moderate intellectual disability and with monoallelic CRMP1 variants. However, one patient with a different monoallelic CRMP1 variant had normal IQ. Hence, this gene should be rated amber with current evidence.
Sources: Literature
Mendeliome v1.2386 CRMP1 Achchuthan Shanmugasundram gene: CRMP1 was added
gene: CRMP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRMP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRMP1 were set to 36511780; 39758889
Phenotypes for gene: CRMP1 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: CRMP1 was set to AMBER
Added comment: PMID:36511780 reported the identification of three different heterozygous de novo variants in the CRMP1 gene (p.(Pro589Leu), p.(Thr427Met) & p.(Phe351Ser)) in three unrelated individuals with a neurodevelopmental disorder presenting with muscular hypotonia, intellectual disability, and/or autism spectrum disorder. ID was moderate in two of them, while IQ was normal in one. There is also functional evidence available for these variants.

PMID:39758889 reported the identification of a novel heterozygous de novo frameshift variant in CRMP1 (p.(Lys586fs)) in a 9-year-old male patient presenting with phenotypes such as autism, language delay, hyperactivity, and learning disabilities. This patient was reported with moderate ID.

There are three unrelated cases reported with moderate intellectual disability and with monoallelic CRMP1 variants. However, one patient with a different monoallelic CRMP1 variant had normal IQ. Hence, this gene should be rated amber with current evidence.
Sources: Literature
Mendeliome v1.2386 GAP43 Achchuthan Shanmugasundram gene: GAP43 was added
gene: GAP43 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GAP43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GAP43 were set to 39738362
Phenotypes for gene: GAP43 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: GAP43 was set to RED
Added comment: PMID:39738362 reported the identification of a heterozygous missense variant in the GAP43 gene (p.(Glu146Lys)) in a 15-year-old female patient with moderate intellectual disability, neurodevelopmental disorders, short stature, and skeletal abnormalities such as left-right difference in legs and digital deformities.

The variant GAP43 protein was found to be unstable in neuronal cells and the disruption of Gap43 in mouse embryonic cortical neurons impaired axonal elongation and dendrite formation.
Sources: Literature
Prepair 1000+ v1.1811 MFRP Zornitza Stark Tag for review tag was added to gene: MFRP.
Prepair 1000+ v1.1811 FAM161A Zornitza Stark Marked gene: FAM161A as ready
Prepair 1000+ v1.1811 FAM161A Zornitza Stark Gene: fam161a has been classified as Red List (Low Evidence).
Prepair 1000+ v1.1811 CBS Zornitza Stark Marked gene: CBS as ready
Prepair 1000+ v1.1811 CBS Zornitza Stark Gene: cbs has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.1811 CBS Zornitza Stark Phenotypes for gene: CBS were changed from Homocystinuria, B6-responsive and nonresponsive types, 236200 (3) to Homocystinuria, B6-responsive and nonresponsive types, MIM#236200
Prepair 1000+ v1.1810 CBS Zornitza Stark Publications for gene: CBS were set to
Prepair 1000+ v1.1809 CBS Zornitza Stark Classified gene: CBS as Amber List (moderate evidence)
Prepair 1000+ v1.1809 CBS Zornitza Stark Gene: cbs has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.1808 CBS Zornitza Stark reviewed gene: CBS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: classic homocystinuria, MONDO:0009352; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1808 ABCC6 Zornitza Stark Marked gene: ABCC6 as ready
Prepair 1000+ v1.1808 ABCC6 Zornitza Stark Gene: abcc6 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.1808 TMEM94 Zornitza Stark Tag for review tag was added to gene: TMEM94.
Prepair 1000+ v1.1808 MBTPS1 Zornitza Stark Tag for review tag was added to gene: MBTPS1.
Prepair 1000+ v1.1808 IGHM Zornitza Stark Tag for review tag was added to gene: IGHM.
Prepair 1000+ v1.1808 DYNC1I2 Zornitza Stark Tag for review tag was added to gene: DYNC1I2.
Prepair 1000+ v1.1808 B9D1 Zornitza Stark Tag for review tag was added to gene: B9D1.
Prepair 1000+ v1.1808 ADPRHL2 Zornitza Stark Tag for review tag was added to gene: ADPRHL2.
Prepair 1000+ v1.1808 ZNHIT3 Zornitza Stark Marked gene: ZNHIT3 as ready
Prepair 1000+ v1.1808 ZNHIT3 Zornitza Stark Gene: znhit3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1808 ZNHIT3 Zornitza Stark Phenotypes for gene: ZNHIT3 were changed from PEHO syndrome, 260565 (3), Autosomal recessive to PEHO syndrome MIM#260565
Prepair 1000+ v1.1807 ZNHIT3 Zornitza Stark Publications for gene: ZNHIT3 were set to
Prepair 1000+ v1.1806 ZNF335 Zornitza Stark Marked gene: ZNF335 as ready
Prepair 1000+ v1.1806 ZNF335 Zornitza Stark Gene: znf335 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1806 ZNF335 Zornitza Stark Phenotypes for gene: ZNF335 were changed from Microcephaly 10, primary, autosomal recessive to Microcephaly 10, primary, autosomal recessive, MIM# 615095
Prepair 1000+ v1.1805 ZNF335 Zornitza Stark Publications for gene: ZNF335 were set to
Prepair 1000+ v1.1804 ZIC3 Zornitza Stark Marked gene: ZIC3 as ready
Prepair 1000+ v1.1804 ZIC3 Zornitza Stark Gene: zic3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1804 ZIC3 Zornitza Stark Phenotypes for gene: ZIC3 were changed from Congenital heart defects, nonsyndromic, 1, X-linked, 306955 (3) to Congenital heart defects, nonsyndromic, 1, X-linked (MIM#306955); Heterotaxy, visceral, 1, X-linked (MIM#306955, MONDO:0010607); VACTERL association, X-linked, MIM# 314390, MONDO:0010752
Prepair 1000+ v1.1803 ZIC3 Zornitza Stark Publications for gene: ZIC3 were set to
Prepair 1000+ v1.1802 ZBTB24 Zornitza Stark Marked gene: ZBTB24 as ready
Prepair 1000+ v1.1802 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1802 ZBTB24 Zornitza Stark Phenotypes for gene: ZBTB24 were changed from Immunodeficiency-centromeric instability-facial anomalies syndrome-2, 614069 (3) to Immunodeficiency-centromeric instability-facial anomalies syndrome 2, MIM# 614069; MONDO:0013553
Prepair 1000+ v1.1801 ZBTB24 Zornitza Stark Publications for gene: ZBTB24 were set to
Prepair 1000+ v1.1800 WDR81 Zornitza Stark Marked gene: WDR81 as ready
Prepair 1000+ v1.1800 WDR81 Zornitza Stark Gene: wdr81 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1800 WDR81 Zornitza Stark Phenotypes for gene: WDR81 were changed from Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2, 610185 (3) to Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2 MIM#610185, MONDO:0012430; Hydrocephalus, congenital, 3, with brain anomalies MIM#617967, MONDO:0054794
Prepair 1000+ v1.1799 WDR81 Zornitza Stark Publications for gene: WDR81 were set to
Prepair 1000+ v1.1798 WDR73 Zornitza Stark Marked gene: WDR73 as ready
Prepair 1000+ v1.1798 WDR73 Zornitza Stark Gene: wdr73 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1798 WDR73 Zornitza Stark Phenotypes for gene: WDR73 were changed from Galloway-Mowat syndrome, 251300 (3) to Galloway-Mowat syndrome 1, MIM# 251300
Prepair 1000+ v1.1797 WDR73 Zornitza Stark Publications for gene: WDR73 were set to
Prepair 1000+ v1.1796 VPS45 Zornitza Stark Marked gene: VPS45 as ready
Prepair 1000+ v1.1796 VPS45 Zornitza Stark Gene: vps45 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1796 VPS45 Zornitza Stark Phenotypes for gene: VPS45 were changed from Neutropenia, severe congenital, 5, autosomal recessive, 615285 (3) to Neutropenia, severe congenital, 5, autosomal recessive, MIM#615285
Prepair 1000+ v1.1795 VPS45 Zornitza Stark Publications for gene: VPS45 were set to
Prepair 1000+ v1.1794 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Prepair 1000+ v1.1794 VPS13B Zornitza Stark Gene: vps13b has been classified as Green List (High Evidence).
Prepair 1000+ v1.1794 VPS13B Zornitza Stark Phenotypes for gene: VPS13B were changed from Cohen syndrome, 216550 (3) to Cohen syndrome, MIM# 216550
Prepair 1000+ v1.1793 VPS13B Zornitza Stark Publications for gene: VPS13B were set to
Prepair 1000+ v1.1792 VARS2 Zornitza Stark Marked gene: VARS2 as ready
Prepair 1000+ v1.1792 VARS2 Zornitza Stark Gene: vars2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1792 VARS2 Zornitza Stark Phenotypes for gene: VARS2 were changed from Combined oxidative phosphorylation deficiency 20, 615917 (3) to Combined oxidative phosphorylation deficiency 20 MIM#615917
Prepair 1000+ v1.1791 VARS2 Zornitza Stark Publications for gene: VARS2 were set to
Prepair 1000+ v1.1790 USH2A Zornitza Stark Marked gene: USH2A as ready
Prepair 1000+ v1.1790 USH2A Zornitza Stark Gene: ush2a has been classified as Green List (High Evidence).
Prepair 1000+ v1.1790 USH2A Zornitza Stark Phenotypes for gene: USH2A were changed from Usher syndrome, type 2A, 276901 (3) to Usher syndrome, type 2A, MIM#276901
Prepair 1000+ v1.1789 USH2A Zornitza Stark Publications for gene: USH2A were set to
Prepair 1000+ v1.1788 UFM1 Zornitza Stark Marked gene: UFM1 as ready
Prepair 1000+ v1.1788 UFM1 Zornitza Stark Gene: ufm1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1788 UFM1 Zornitza Stark Phenotypes for gene: UFM1 were changed from Leukodystrophy, hypomyelinating, 14, 617899 (3), Autosomal recessive to Leukodystrophy, hypomyelinating, 14, MIM#617899
Prepair 1000+ v1.1787 UFM1 Zornitza Stark Publications for gene: UFM1 were set to
Prepair 1000+ v1.1786 TYMP Zornitza Stark Marked gene: TYMP as ready
Prepair 1000+ v1.1786 TYMP Zornitza Stark Gene: tymp has been classified as Green List (High Evidence).
Prepair 1000+ v1.1786 TYMP Zornitza Stark Phenotypes for gene: TYMP were changed from Mitochondrial DNA depletion syndrome 1 (MNGIE type), 603041 (3) to Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM#603041
Prepair 1000+ v1.1785 TYMP Zornitza Stark Publications for gene: TYMP were set to
Prepair 1000+ v1.1784 TTC7A Zornitza Stark Marked gene: TTC7A as ready
Prepair 1000+ v1.1784 TTC7A Zornitza Stark Gene: ttc7a has been classified as Green List (High Evidence).
Prepair 1000+ v1.1784 TTC7A Zornitza Stark Phenotypes for gene: TTC7A were changed from Gastrointestinal defects and immunodeficiency syndrome, 243150 (3) to Gastrointestinal defects and immunodeficiency syndrome MIM#243150
Prepair 1000+ v1.1783 TTC7A Zornitza Stark Publications for gene: TTC7A were set to
Prepair 1000+ v1.1782 TTC37 Zornitza Stark Marked gene: TTC37 as ready
Prepair 1000+ v1.1782 TTC37 Zornitza Stark Gene: ttc37 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1782 TTC37 Zornitza Stark Phenotypes for gene: TTC37 were changed from Trichohepatoenteric syndrome 1, 222470 (3) to Trichohepatoenteric syndrome 1 MIM#222470
Prepair 1000+ v1.1781 TTC37 Zornitza Stark Publications for gene: TTC37 were set to
Prepair 1000+ v1.1780 TMEM237 Zornitza Stark Marked gene: TMEM237 as ready
Prepair 1000+ v1.1780 TMEM237 Zornitza Stark Gene: tmem237 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1780 TMEM237 Zornitza Stark Phenotypes for gene: TMEM237 were changed from Joubert syndrome 14, 614424 (3) to Joubert syndrome 14, MIM#614424
Prepair 1000+ v1.1779 TMEM237 Zornitza Stark Publications for gene: TMEM237 were set to
Prepair 1000+ v1.1778 TMEM231 Zornitza Stark Marked gene: TMEM231 as ready
Prepair 1000+ v1.1778 TMEM231 Zornitza Stark Gene: tmem231 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1778 TMEM231 Zornitza Stark Phenotypes for gene: TMEM231 were changed from Joubert syndrome 20, 614970 (3) to Joubert syndrome 20, MIM#614970; Meckel syndrome 11, MIM#615397
Prepair 1000+ v1.1777 TMEM231 Zornitza Stark Publications for gene: TMEM231 were set to
Prepair 1000+ v1.1776 TMEM165 Zornitza Stark Marked gene: TMEM165 as ready
Prepair 1000+ v1.1776 TMEM165 Zornitza Stark Gene: tmem165 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1776 TMEM165 Zornitza Stark Phenotypes for gene: TMEM165 were changed from Congenital disorder of glycosylation, type IIk, 614727 (3) to Congenital disorder of glycosylation, type IIk, MIM#614727
Prepair 1000+ v1.1775 TMEM165 Zornitza Stark Publications for gene: TMEM165 were set to
Prepair 1000+ v1.1774 TJP2 Zornitza Stark Marked gene: TJP2 as ready
Prepair 1000+ v1.1774 TJP2 Zornitza Stark Gene: tjp2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1774 TJP2 Zornitza Stark Phenotypes for gene: TJP2 were changed from Cholestasis, progressive familial intrahepatic 4, 615878 (3) to Cholestasis, progressive familial intrahepatic 4, MIM# 615878
Prepair 1000+ v1.1773 TJP2 Zornitza Stark Publications for gene: TJP2 were set to
Prepair 1000+ v1.1772 TCN2 Zornitza Stark Marked gene: TCN2 as ready
Prepair 1000+ v1.1772 TCN2 Zornitza Stark Gene: tcn2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1772 TCN2 Zornitza Stark Phenotypes for gene: TCN2 were changed from Transcobalamin II deficiency, 275350 (3) to Transcobalamin II deficiency MIM#275350
Prepair 1000+ v1.1771 TCN2 Zornitza Stark Publications for gene: TCN2 were set to
Prepair 1000+ v1.1770 TBX19 Zornitza Stark Marked gene: TBX19 as ready
Prepair 1000+ v1.1770 TBX19 Zornitza Stark Gene: tbx19 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1770 TBX19 Zornitza Stark Phenotypes for gene: TBX19 were changed from Adrenocorticotropic hormone deficiency, 201400 (3) to Adrenocorticotropic hormone deficiency, MIM# 201400
Prepair 1000+ v1.1769 TBX19 Zornitza Stark Publications for gene: TBX19 were set to
Prepair 1000+ v1.1768 TBCK Zornitza Stark Marked gene: TBCK as ready
Prepair 1000+ v1.1768 TBCK Zornitza Stark Gene: tbck has been classified as Green List (High Evidence).
Prepair 1000+ v1.1768 TBCK Zornitza Stark Phenotypes for gene: TBCK were changed from Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, 616900 (3), Autosomal recessive to Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, MIM# 616900
Prepair 1000+ v1.1767 TBCK Zornitza Stark Publications for gene: TBCK were set to
Prepair 1000+ v1.1766 STRADA Zornitza Stark Marked gene: STRADA as ready
Prepair 1000+ v1.1766 STRADA Zornitza Stark Gene: strada has been classified as Green List (High Evidence).
Prepair 1000+ v1.1766 STRADA Zornitza Stark Phenotypes for gene: STRADA were changed from Polyhydramnios, megalencephaly, and symptomatic epilepsy, 611087 (3), Autosomal recessive to Polyhydramnios, megalencephaly, and symptomatic epilepsy MIM#611087
Prepair 1000+ v1.1765 STRADA Zornitza Stark Publications for gene: STRADA were set to
Prepair 1000+ v1.1764 STAT1 Zornitza Stark Marked gene: STAT1 as ready
Prepair 1000+ v1.1764 STAT1 Zornitza Stark Gene: stat1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1764 STAT1 Zornitza Stark Phenotypes for gene: STAT1 were changed from Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive, 613796 (3) to Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive MIM#613796; Immunodeficiency 31B MONDO:0013427
Prepair 1000+ v1.1763 STAT1 Zornitza Stark Publications for gene: STAT1 were set to
Prepair 1000+ v1.1762 ST3GAL5 Zornitza Stark Marked gene: ST3GAL5 as ready
Prepair 1000+ v1.1762 ST3GAL5 Zornitza Stark Gene: st3gal5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1762 ST3GAL5 Zornitza Stark Phenotypes for gene: ST3GAL5 were changed from Salt and pepper developmental regression syndrome, 609056 (3), Autosomal recessive to Salt and pepper developmental regression syndrome, MIM# 609056
Prepair 1000+ v1.1761 ST3GAL5 Zornitza Stark Publications for gene: ST3GAL5 were set to
Prepair 1000+ v1.1760 SSR4 Zornitza Stark Marked gene: SSR4 as ready
Prepair 1000+ v1.1760 SSR4 Zornitza Stark Gene: ssr4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1760 SSR4 Zornitza Stark Phenotypes for gene: SSR4 were changed from Congenital disorder of glycosylation, type Iy, 300934 (3), X-linked recessive to Congenital disorder of glycosylation, type Iy MIM#300934
Prepair 1000+ v1.1759 SSR4 Zornitza Stark Publications for gene: SSR4 were set to
Prepair 1000+ v1.1758 SPINT2 Zornitza Stark Marked gene: SPINT2 as ready
Prepair 1000+ v1.1758 SPINT2 Zornitza Stark Gene: spint2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1758 SPINT2 Zornitza Stark Phenotypes for gene: SPINT2 were changed from Diarrhea 3, secretory sodium, congenital, syndromic, 270420 (3) to Diarrhoea 3, secretory sodium, congenital, syndromic, MIM#270420
Prepair 1000+ v1.1757 SPINT2 Zornitza Stark Publications for gene: SPINT2 were set to
Prepair 1000+ v1.1756 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Prepair 1000+ v1.1756 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1756 SPATA5 Zornitza Stark Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome, 616577 (3), Autosomal recessive to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, MIM# 616577
Prepair 1000+ v1.1755 SPATA5 Zornitza Stark Publications for gene: SPATA5 were set to
Prepair 1000+ v1.1754 SMARCAL1 Zornitza Stark Marked gene: SMARCAL1 as ready
Prepair 1000+ v1.1754 SMARCAL1 Zornitza Stark Gene: smarcal1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1754 SMARCAL1 Zornitza Stark Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia, 242900 (3) to Schimke immunoosseous dysplasia, MIM# 242900
Prepair 1000+ v1.1753 SMARCAL1 Zornitza Stark Publications for gene: SMARCAL1 were set to
Prepair 1000+ v1.1752 SLC6A8 Zornitza Stark Marked gene: SLC6A8 as ready
Prepair 1000+ v1.1752 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1752 SLC6A8 Zornitza Stark Phenotypes for gene: SLC6A8 were changed from Cerebral creatine deficiency syndrome 1, 300352 (3) to Cerebral creatine deficiency syndrome 1, MIM#300352
Prepair 1000+ v1.1751 SLC6A8 Zornitza Stark Publications for gene: SLC6A8 were set to
Prepair 1000+ v1.1750 SLC6A5 Zornitza Stark Marked gene: SLC6A5 as ready
Prepair 1000+ v1.1750 SLC6A5 Zornitza Stark Gene: slc6a5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1750 SLC6A5 Zornitza Stark Phenotypes for gene: SLC6A5 were changed from Hyperekplexia 3, 614618 (3) to Hyperekplexia 3 MIM#614618
Prepair 1000+ v1.1749 SLC6A5 Zornitza Stark Publications for gene: SLC6A5 were set to
Prepair 1000+ v1.1748 SLC52A3 Zornitza Stark Marked gene: SLC52A3 as ready
Prepair 1000+ v1.1748 SLC52A3 Zornitza Stark Gene: slc52a3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1748 SLC52A3 Zornitza Stark Phenotypes for gene: SLC52A3 were changed from Brown-Vialetto-Van Laere syndrome 1, 211530 (3) to Brown-Vialetto-Van Laere syndrome 1, MIM#211530
Prepair 1000+ v1.1747 SLC52A3 Zornitza Stark Publications for gene: SLC52A3 were set to
Prepair 1000+ v1.1746 SLC52A2 Zornitza Stark Marked gene: SLC52A2 as ready
Prepair 1000+ v1.1746 SLC52A2 Zornitza Stark Gene: slc52a2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1746 SLC52A2 Zornitza Stark Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2, 614707 (3) to Brown-Vialetto-Van Laere syndrome 2, MIM# 614707
Prepair 1000+ v1.1745 SLC52A2 Zornitza Stark Publications for gene: SLC52A2 were set to
Prepair 1000+ v1.1744 SLC4A4 Zornitza Stark Marked gene: SLC4A4 as ready
Prepair 1000+ v1.1744 SLC4A4 Zornitza Stark Gene: slc4a4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1744 SLC4A4 Zornitza Stark Phenotypes for gene: SLC4A4 were changed from Renal tubular acidosis, proximal, with ocular abnormalities, 604278 (3) to Renal tubular acidosis, proximal, with ocular abnormalities, MIM#604278
Prepair 1000+ v1.1743 SLC4A4 Zornitza Stark Publications for gene: SLC4A4 were set to
Prepair 1000+ v1.1742 SLC4A1 Zornitza Stark Phenotypes for gene: SLC4A1 were changed from Distal renal tubular acidosis 4 with hemolytic anemia, MIM# 611590 to Distal renal tubular acidosis 4 with haemolytic anaemia, MIM# 611590
Prepair 1000+ v1.1741 SLC4A1 Zornitza Stark Marked gene: SLC4A1 as ready
Prepair 1000+ v1.1741 SLC4A1 Zornitza Stark Gene: slc4a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1741 SLC4A1 Zornitza Stark Phenotypes for gene: SLC4A1 were changed from Renal tubular acidosis, distal, AR, 611590 (3) to Distal renal tubular acidosis 4 with hemolytic anemia, MIM# 611590
Prepair 1000+ v1.1740 SLC4A1 Zornitza Stark Publications for gene: SLC4A1 were set to
Prepair 1000+ v1.1739 SLC33A1 Zornitza Stark Marked gene: SLC33A1 as ready
Prepair 1000+ v1.1739 SLC33A1 Zornitza Stark Gene: slc33a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1739 SLC33A1 Zornitza Stark Phenotypes for gene: SLC33A1 were changed from Congenital cataracts, hearing loss, and neurodegeneration, 614482 (3) to Congenital cataracts, hearing loss, and neurodegeneration, MIM#614482
Prepair 1000+ v1.1738 SLC33A1 Zornitza Stark Publications for gene: SLC33A1 were set to
Prepair 1000+ v1.1737 SLC26A3 Zornitza Stark Marked gene: SLC26A3 as ready
Prepair 1000+ v1.1737 SLC26A3 Zornitza Stark Gene: slc26a3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1737 SLC26A3 Zornitza Stark Phenotypes for gene: SLC26A3 were changed from Diarrhea 1, secretory chloride, congenital, 214700 (3) to Diarrhoea 1, secretory chloride, congenital MIM#214700
Prepair 1000+ v1.1736 SLC26A3 Zornitza Stark Publications for gene: SLC26A3 were set to
Prepair 1000+ v1.1735 SLC25A13 Zornitza Stark Marked gene: SLC25A13 as ready
Prepair 1000+ v1.1735 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1735 SLC25A13 Zornitza Stark Publications for gene: SLC25A13 were set to
Regression v0.574 KLC4 Zornitza Stark Marked gene: KLC4 as ready
Regression v0.574 KLC4 Zornitza Stark Gene: klc4 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.1734 SKIV2L Zornitza Stark Marked gene: SKIV2L as ready
Prepair 1000+ v1.1734 SKIV2L Zornitza Stark Gene: skiv2l has been classified as Green List (High Evidence).
Prepair 1000+ v1.1734 SKIV2L Zornitza Stark Phenotypes for gene: SKIV2L were changed from Trichohepatoenteric syndrome 2, 614602 (3) to Trichohepatoenteric syndrome 2, MIM# 614602
Prepair 1000+ v1.1733 SKIV2L Zornitza Stark Publications for gene: SKIV2L were set to
Prepair 1000+ v1.1732 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Prepair 1000+ v1.1732 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1732 SIL1 Zornitza Stark Phenotypes for gene: SIL1 were changed from Marinesco-Sjogren syndrome, 248800 (3) to Marinesco-Sjogren syndrome MIM#248800
Prepair 1000+ v1.1731 SIL1 Zornitza Stark Publications for gene: SIL1 were set to
Prepair 1000+ v1.1730 SERPINH1 Zornitza Stark Marked gene: SERPINH1 as ready
Prepair 1000+ v1.1730 SERPINH1 Zornitza Stark Gene: serpinh1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1730 SERPINH1 Zornitza Stark Phenotypes for gene: SERPINH1 were changed from Orofaciodigital syndrome VI, 277170 (3) to Osteogenesis imperfecta, type X, MIM# 613848; Osteogenesis imperfecta type 10, MONDO:0013459
Prepair 1000+ v1.1729 SERPINH1 Zornitza Stark Publications for gene: SERPINH1 were set to
Prepair 1000+ v1.1728 SEPSECS Zornitza Stark Marked gene: SEPSECS as ready
Prepair 1000+ v1.1728 SEPSECS Zornitza Stark Gene: sepsecs has been classified as Green List (High Evidence).
Prepair 1000+ v1.1728 SEPSECS Zornitza Stark Phenotypes for gene: SEPSECS were changed from Pontocerebellar hypoplasia type 2D, 613811 (3) to Pontocerebellar hypoplasia type 2D, MIM# 613811
Prepair 1000+ v1.1727 SEPSECS Zornitza Stark Publications for gene: SEPSECS were set to
Prepair 1000+ v1.1726 SELENON Zornitza Stark Marked gene: SELENON as ready
Prepair 1000+ v1.1726 SELENON Zornitza Stark Gene: selenon has been classified as Green List (High Evidence).
Prepair 1000+ v1.1726 SELENON Zornitza Stark Phenotypes for gene: SELENON were changed from Muscular dystrophy, rigid spine, 1, 602771 (3) to Congenital myopathy 3 with rigid spine, MIM# 602771
Prepair 1000+ v1.1725 SELENON Zornitza Stark Publications for gene: SELENON were set to
Prepair 1000+ v1.1724 SCNN1A Zornitza Stark Marked gene: SCNN1A as ready
Prepair 1000+ v1.1724 SCNN1A Zornitza Stark Gene: scnn1a has been classified as Green List (High Evidence).
Prepair 1000+ v1.1724 SCNN1A Zornitza Stark Phenotypes for gene: SCNN1A were changed from Pseudohypoaldosteronism, type I, 264350 (3) to Pseudohypoaldosteronism, type IB1, autosomal recessive, MIM# 264350
Prepair 1000+ v1.1723 SCNN1A Zornitza Stark Publications for gene: SCNN1A were set to
Prepair 1000+ v1.1722 RSPH4A Zornitza Stark Marked gene: RSPH4A as ready
Prepair 1000+ v1.1722 RSPH4A Zornitza Stark Gene: rsph4a has been classified as Green List (High Evidence).
Prepair 1000+ v1.1722 RSPH4A Zornitza Stark Phenotypes for gene: RSPH4A were changed from Ciliary dyskinesia, primary, 11, 612649 (3) to Ciliary dyskinesia, primary, 11, MIM# 612649
Prepair 1000+ v1.1721 RSPH4A Zornitza Stark Publications for gene: RSPH4A were set to
Prepair 1000+ v1.1720 PSPH Zornitza Stark Marked gene: PSPH as ready
Prepair 1000+ v1.1720 PSPH Zornitza Stark Gene: psph has been classified as Green List (High Evidence).
Prepair 1000+ v1.1720 PSPH Zornitza Stark Phenotypes for gene: PSPH were changed from Phosphoserine phosphatase deficiency, 614023 (3) to Phosphoserine phosphatase deficiency , MIM# 614023
Prepair 1000+ v1.1719 PSPH Zornitza Stark Publications for gene: PSPH were set to
Prepair 1000+ v1.1718 PPT1 Zornitza Stark Marked gene: PPT1 as ready
Prepair 1000+ v1.1718 PPT1 Zornitza Stark Gene: ppt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1718 PPT1 Zornitza Stark Phenotypes for gene: PPT1 were changed from Ceroid lipofuscinosis, neuronal, 1, 256730 (3) to Ceroid lipofuscinosis, neuronal, 1, MIM# 256730
Prepair 1000+ v1.1717 PPT1 Zornitza Stark Publications for gene: PPT1 were set to
Prepair 1000+ v1.1716 POMK Zornitza Stark Marked gene: POMK as ready
Prepair 1000+ v1.1716 POMK Zornitza Stark Gene: pomk has been classified as Green List (High Evidence).
Prepair 1000+ v1.1716 POMK Zornitza Stark Phenotypes for gene: POMK were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, 615249 (3) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, MIM#615249
Prepair 1000+ v1.1715 POMK Zornitza Stark Publications for gene: POMK were set to
Prepair 1000+ v1.1714 POLR3A Zornitza Stark Marked gene: POLR3A as ready
Prepair 1000+ v1.1714 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Prepair 1000+ v1.1714 POLR3A Zornitza Stark Phenotypes for gene: POLR3A were changed from Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, 607694 (3) to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694; Wiedemann-Rautenstrauch syndrome, MIM# 264090
Prepair 1000+ v1.1713 POLR3A Zornitza Stark Publications for gene: POLR3A were set to
Prepair 1000+ v1.1712 PLOD1 Zornitza Stark Marked gene: PLOD1 as ready
Prepair 1000+ v1.1712 PLOD1 Zornitza Stark Gene: plod1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1712 PLOD1 Zornitza Stark Phenotypes for gene: PLOD1 were changed from Ehlers-Danlos syndrome, type VI, 225400 (3) to Ehlers-Danlos syndrome, kyphoscoliotic type, 1, MIM# 225400
Prepair 1000+ v1.1711 PLOD1 Zornitza Stark Publications for gene: PLOD1 were set to
Prepair 1000+ v1.1710 PLEC Zornitza Stark Marked gene: PLEC as ready
Prepair 1000+ v1.1710 PLEC Zornitza Stark Gene: plec has been classified as Green List (High Evidence).
Prepair 1000+ v1.1710 PLEC Zornitza Stark Phenotypes for gene: PLEC were changed from Epidermolysis bullosa simplex with pyloric atresia, 612138 (3) to Epidermolysis bullosa simplex 5D, generalized intermediate, autosomal recessive, MIM# 616487; Epidermolysis bullosa simplex 5B, with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex 5C, with pyloric atresia MIM# 612138; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723
Prepair 1000+ v1.1709 PLEC Zornitza Stark Publications for gene: PLEC were set to
Prepair 1000+ v1.1708 PFKM Zornitza Stark Marked gene: PFKM as ready
Prepair 1000+ v1.1708 PFKM Zornitza Stark Gene: pfkm has been classified as Green List (High Evidence).
Prepair 1000+ v1.1708 PFKM Zornitza Stark Phenotypes for gene: PFKM were changed from Glycogen storage disease VII, 232800 (3) to Glycogen storage disease VII MIM#232800
Prepair 1000+ v1.1707 PFKM Zornitza Stark Publications for gene: PFKM were set to
Prepair 1000+ v1.1706 PEX6 Zornitza Stark Marked gene: PEX6 as ready
Prepair 1000+ v1.1706 PEX6 Zornitza Stark Gene: pex6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1706 PEX6 Zornitza Stark Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A (Zellweger), 614862 to Peroxisome biogenesis disorder 4A (Zellweger), MIM# 614862; Peroxisome biogenesis disorder-4B, MIM# 614863
Prepair 1000+ v1.1705 PEX6 Zornitza Stark Publications for gene: PEX6 were set to
Prepair 1000+ v1.1704 PEX13 Zornitza Stark Marked gene: PEX13 as ready
Prepair 1000+ v1.1704 PEX13 Zornitza Stark Gene: pex13 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1704 PEX13 Zornitza Stark Phenotypes for gene: PEX13 were changed from Peroxisome biogenesis disorder 11A (Zellweger), 614883 to Peroxisome biogenesis disorder 11A (Zellweger), MIM#614883; Peroxisome biogenesis disorder 11B, MIM#614885
Prepair 1000+ v1.1703 PEX12 Zornitza Stark Marked gene: PEX12 as ready
Prepair 1000+ v1.1703 PEX12 Zornitza Stark Gene: pex12 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1703 PEX12 Zornitza Stark Phenotypes for gene: PEX12 were changed from Peroxisome biogenesis disorder 3A (Zellweger), 614859 to Peroxisome biogenesis disorder 3A (Zellweger), MIM#614859; Peroxisome biogenesis disorder 3B, MIM#266510
Prepair 1000+ v1.1702 PEPD Zornitza Stark Marked gene: PEPD as ready
Prepair 1000+ v1.1702 PEPD Zornitza Stark Gene: pepd has been classified as Green List (High Evidence).
Prepair 1000+ v1.1702 PEPD Zornitza Stark Phenotypes for gene: PEPD were changed from Prolidase deficiency, 170100 (3) to Prolidase deficiency, MIM# 170100
Prepair 1000+ v1.1701 PEPD Zornitza Stark Publications for gene: PEPD were set to
Prepair 1000+ v1.1700 P3H1 Zornitza Stark Marked gene: P3H1 as ready
Prepair 1000+ v1.1700 P3H1 Zornitza Stark Gene: p3h1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1700 P3H1 Zornitza Stark Phenotypes for gene: P3H1 were changed from Osteogenesis imperfecta, type VIII, 610915 (3) to Osteogenesis imperfecta, type VIII, MIM#610915
Prepair 1000+ v1.1699 P3H1 Zornitza Stark Publications for gene: P3H1 were set to
Prepair 1000+ v1.1698 OTC Zornitza Stark Marked gene: OTC as ready
Prepair 1000+ v1.1698 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Prepair 1000+ v1.1698 OTC Zornitza Stark Phenotypes for gene: OTC were changed from Ornithine transcarbamylase deficiency, 311250 (3) to Ornithine transcarbamylase deficiency, MIM# 311250
Prepair 1000+ v1.1697 OTC Zornitza Stark Publications for gene: OTC were set to
Prepair 1000+ v1.1696 ORC6 Zornitza Stark Marked gene: ORC6 as ready
Prepair 1000+ v1.1696 ORC6 Zornitza Stark Gene: orc6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1696 ORC6 Zornitza Stark Phenotypes for gene: ORC6 were changed from Meier-Gorlin syndrome 3, 613803 (3) to Meier-Gorlin syndrome 3 MIM#613803
Prepair 1000+ v1.1695 ORC6 Zornitza Stark Publications for gene: ORC6 were set to
Prepair 1000+ v1.1694 ORAI1 Zornitza Stark Marked gene: ORAI1 as ready
Prepair 1000+ v1.1694 ORAI1 Zornitza Stark Gene: orai1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1694 ORAI1 Zornitza Stark Phenotypes for gene: ORAI1 were changed from Immunodeficiency 9, 612782 (3) to Immunodeficiency 9, MIM#612782; Myopathy, tubular aggregate, 2, MIM#615883
Prepair 1000+ v1.1693 ORAI1 Zornitza Stark Publications for gene: ORAI1 were set to
Prepair 1000+ v1.1692 OPHN1 Zornitza Stark Marked gene: OPHN1 as ready
Prepair 1000+ v1.1692 OPHN1 Zornitza Stark Gene: ophn1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1692 OPHN1 Zornitza Stark Phenotypes for gene: OPHN1 were changed from Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, 300486 (3) to Intellectual developmental disorder, X-linked syndromic, Billuart type MIM#300486; X-linked intellectual disability-cerebellar hypoplasia syndrome MONDO:0010337
Prepair 1000+ v1.1691 OPHN1 Zornitza Stark Publications for gene: OPHN1 were set to
Prepair 1000+ v1.1690 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Prepair 1000+ v1.1690 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1690 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from Joubert syndrome 10, 300804 (3) to Joubert syndrome 10 MIM#300804; Simpson-Golabi-Behmel syndrome, type 2 MIM#300209
Prepair 1000+ v1.1689 OFD1 Zornitza Stark Publications for gene: OFD1 were set to
Prepair 1000+ v1.1688 NYX Zornitza Stark Marked gene: NYX as ready
Prepair 1000+ v1.1688 NYX Zornitza Stark Gene: nyx has been classified as Green List (High Evidence).
Prepair 1000+ v1.1688 NYX Zornitza Stark Phenotypes for gene: NYX were changed from Night blindness, congenital stationary (complete), 1A, X-linked, MIM #310500 to Night blindness, congenital stationary (complete), 1A, X-linked MIM310500
Prepair 1000+ v1.1687 NYX Zornitza Stark Publications for gene: NYX were set to
Prepair 1000+ v1.1686 NT5C2 Zornitza Stark Marked gene: NT5C2 as ready
Prepair 1000+ v1.1686 NT5C2 Zornitza Stark Gene: nt5c2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1686 NT5C2 Zornitza Stark Phenotypes for gene: NT5C2 were changed from Spastic paraplegia 45, 613162 (3) to Spastic paraplegia 45, autosomal recessive, MIM# 613162
Prepair 1000+ v1.1685 NT5C2 Zornitza Stark Publications for gene: NT5C2 were set to
Prepair 1000+ v1.1684 NSUN2 Zornitza Stark Marked gene: NSUN2 as ready
Prepair 1000+ v1.1684 NSUN2 Zornitza Stark Gene: nsun2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1684 NSUN2 Zornitza Stark Phenotypes for gene: NSUN2 were changed from Mental retardation, autosomal recessive 5, 611091 (3) to Intellectual developmental disorder, autosomal recessive 5, MIM# 611091
Prepair 1000+ v1.1683 NSUN2 Zornitza Stark Publications for gene: NSUN2 were set to
Prepair 1000+ v1.1682 NPHS2 Zornitza Stark Marked gene: NPHS2 as ready
Prepair 1000+ v1.1682 NPHS2 Zornitza Stark Gene: nphs2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1682 NPHS2 Zornitza Stark Phenotypes for gene: NPHS2 were changed from Nephrotic syndrome, type 2, 600995 (3) to Nephrotic syndrome, type 2 MIM#600995
Prepair 1000+ v1.1681 NPHS2 Zornitza Stark Publications for gene: NPHS2 were set to
Prepair 1000+ v1.1680 NIPAL4 Zornitza Stark Marked gene: NIPAL4 as ready
Prepair 1000+ v1.1680 NIPAL4 Zornitza Stark Gene: nipal4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1680 NIPAL4 Zornitza Stark Phenotypes for gene: NIPAL4 were changed from Ichthyosis, congenital, autosomal recessive 6, 612281 (3) to Ichthyosis, congenital, autosomal recessive 6 MIM#612281
Prepair 1000+ v1.1679 NIPAL4 Zornitza Stark Publications for gene: NIPAL4 were set to
Prepair 1000+ v1.1678 NHS Zornitza Stark Marked gene: NHS as ready
Prepair 1000+ v1.1678 NHS Zornitza Stark Gene: nhs has been classified as Green List (High Evidence).
Prepair 1000+ v1.1678 NHS Zornitza Stark Phenotypes for gene: NHS were changed from Cataract 40, X-linked, 302200 (3) to Nance-Horan syndrome MIM#302350
Prepair 1000+ v1.1677 NHS Zornitza Stark Publications for gene: NHS were set to
Prepair 1000+ v1.1676 NHS Zornitza Stark reviewed gene: NHS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nance-Horan syndrome MIM#302350; Mode of inheritance: None
Prepair 1000+ v1.1676 NEK8 Zornitza Stark Marked gene: NEK8 as ready
Prepair 1000+ v1.1676 NEK8 Zornitza Stark Gene: nek8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1676 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, 615415 (3), Autosomal recessive to Renal-hepatic-pancreatic dysplasia 2 MIM#615415
Prepair 1000+ v1.1675 NEK8 Zornitza Stark Publications for gene: NEK8 were set to
Prepair 1000+ v1.1674 NDUFS1 Zornitza Stark Marked gene: NDUFS1 as ready
Prepair 1000+ v1.1674 NDUFS1 Zornitza Stark Gene: ndufs1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1674 NDUFS1 Zornitza Stark Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 5, MIM#618226
Prepair 1000+ v1.1673 NDUFS1 Zornitza Stark Publications for gene: NDUFS1 were set to
Prepair 1000+ v1.1672 NAXE Zornitza Stark Marked gene: NAXE as ready
Prepair 1000+ v1.1672 NAXE Zornitza Stark Gene: naxe has been classified as Green List (High Evidence).
Prepair 1000+ v1.1672 NAXE Zornitza Stark Phenotypes for gene: NAXE were changed from Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 617186 (3), Autosomal recessive to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, MIM #617186
Prepair 1000+ v1.1671 NAXE Zornitza Stark Publications for gene: NAXE were set to
Prepair 1000+ v1.1670 MPLKIP Zornitza Stark Marked gene: MPLKIP as ready
Prepair 1000+ v1.1670 MPLKIP Zornitza Stark Gene: mplkip has been classified as Green List (High Evidence).
Prepair 1000+ v1.1670 MPLKIP Zornitza Stark Phenotypes for gene: MPLKIP were changed from Trichothiodystrophy 4, nonphotosensitive, 234050 (3) to Trichothiodystrophy 4, nonphotosensitive MIM#234050
Prepair 1000+ v1.1669 MPLKIP Zornitza Stark Publications for gene: MPLKIP were set to
Prepair 1000+ v1.1668 MMAB Zornitza Stark Marked gene: MMAB as ready
Prepair 1000+ v1.1668 MMAB Zornitza Stark Gene: mmab has been classified as Green List (High Evidence).
Prepair 1000+ v1.1668 MMAB Zornitza Stark Phenotypes for gene: MMAB were changed from Methylmalonic aciduria, vitamin B12-responsive, due to defect in synthesis of adenosylcobalamin, cblB complementation type, 251110 (3) to Methylmalonic aciduria, vitamin B12-responsive, cblB type MIM#251110
Prepair 1000+ v1.1667 MMAB Zornitza Stark Publications for gene: MMAB were set to
Prepair 1000+ v1.1666 MGAT2 Zornitza Stark Marked gene: MGAT2 as ready
Prepair 1000+ v1.1666 MGAT2 Zornitza Stark Gene: mgat2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1666 MGAT2 Zornitza Stark Phenotypes for gene: MGAT2 were changed from Congenital disorder of glycosylation, type IIa, 212066 (3) to Congenital disorder of glycosylation, type IIa MIM#212066
Prepair 1000+ v1.1665 MGAT2 Zornitza Stark Publications for gene: MGAT2 were set to
Prepair 1000+ v1.1664 MCFD2 Zornitza Stark Marked gene: MCFD2 as ready
Prepair 1000+ v1.1664 MCFD2 Zornitza Stark Gene: mcfd2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1664 MCFD2 Zornitza Stark Phenotypes for gene: MCFD2 were changed from Factor V and factor VIII, combined deficiency of, 613625 (3) to Factor V and factor VIII, combined deficiency of MIM#613625
Prepair 1000+ v1.1663 MCFD2 Zornitza Stark Publications for gene: MCFD2 were set to
Prepair 1000+ v1.1662 MCFD2 Zornitza Stark reviewed gene: MCFD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor V and factor VIII, combined deficiency of MIM#613625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1662 MALT1 Zornitza Stark Marked gene: MALT1 as ready
Prepair 1000+ v1.1662 MALT1 Zornitza Stark Gene: malt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1662 MALT1 Zornitza Stark Phenotypes for gene: MALT1 were changed from Immunodeficiency 12, 615468 (3) to Immunodeficiency 12 MIM#615468
Prepair 1000+ v1.1661 MALT1 Zornitza Stark Publications for gene: MALT1 were set to
Prepair 1000+ v1.1660 LTBP4 Zornitza Stark Marked gene: LTBP4 as ready
Prepair 1000+ v1.1660 LTBP4 Zornitza Stark Gene: ltbp4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1660 LTBP4 Zornitza Stark Phenotypes for gene: LTBP4 were changed from Cutis laxa, autosomal recessive, type IC, 613177 (3) to Cutis laxa, autosomal recessive, type IC, #613177
Prepair 1000+ v1.1659 LTBP4 Zornitza Stark Publications for gene: LTBP4 were set to
Prepair 1000+ v1.1658 LTBP3 Zornitza Stark Marked gene: LTBP3 as ready
Prepair 1000+ v1.1658 LTBP3 Zornitza Stark Gene: ltbp3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1658 LTBP3 Zornitza Stark Phenotypes for gene: LTBP3 were changed from Tooth agenesis, selective, 6, 613097 (3) to Dental anomalies and short stature, MIM #601216
Prepair 1000+ v1.1657 LTBP3 Zornitza Stark Publications for gene: LTBP3 were set to
Prepair 1000+ v1.1656 LRP5 Zornitza Stark Marked gene: LRP5 as ready
Prepair 1000+ v1.1656 LRP5 Zornitza Stark Added comment: Comment when marking as ready: Prepair only screens for recessive conditions.
Prepair 1000+ v1.1656 LRP5 Zornitza Stark Gene: lrp5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1656 LRP5 Zornitza Stark Phenotypes for gene: LRP5 were changed from Osteoporosis-pseudoglioma syndrome, 259770 (3) to Exudative vitreoretinopathy 4 MIM#601813; Osteoporosis-pseudoglioma syndrome MIM#259770
Prepair 1000+ v1.1655 LRP5 Zornitza Stark Publications for gene: LRP5 were set to
Prepair 1000+ v1.1654 LRP2 Zornitza Stark Marked gene: LRP2 as ready
Prepair 1000+ v1.1654 LRP2 Zornitza Stark Gene: lrp2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1654 LRP2 Zornitza Stark Phenotypes for gene: LRP2 were changed from Donnai-Barrow syndrome, 222448 (3) to Donnai-Barrow syndrome, MIM #222448
Prepair 1000+ v1.1653 LRP2 Zornitza Stark Publications for gene: LRP2 were set to
Prepair 1000+ v1.1652 LRIG2 Zornitza Stark Marked gene: LRIG2 as ready
Prepair 1000+ v1.1652 LRIG2 Zornitza Stark Gene: lrig2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1652 LRIG2 Zornitza Stark Phenotypes for gene: LRIG2 were changed from Urofacial syndrome 2, 615112 (3) to Urofacial syndrome 2, MIM #615112
Prepair 1000+ v1.1651 LRIG2 Zornitza Stark Publications for gene: LRIG2 were set to
Prepair 1000+ v1.1650 LIPT1 Zornitza Stark Marked gene: LIPT1 as ready
Prepair 1000+ v1.1650 LIPT1 Zornitza Stark Gene: lipt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1650 LIPT1 Zornitza Stark Phenotypes for gene: LIPT1 were changed from Lipoyltransferase 1 deficiency, 616299 (3) to Lipoyltransferase 1 deficiency, MIM#616299
Prepair 1000+ v1.1649 LIPT1 Zornitza Stark Publications for gene: LIPT1 were set to
Prepair 1000+ v1.1648 LIPT1 Zornitza Stark reviewed gene: LIPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681092; Phenotypes: Lipoyltransferase 1 deficiency, MIM#616299; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1648 LAMB3 Zornitza Stark Marked gene: LAMB3 as ready
Prepair 1000+ v1.1648 LAMB3 Zornitza Stark Gene: lamb3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1648 LAMB3 Zornitza Stark Phenotypes for gene: LAMB3 were changed from Epidermolysis bullosa, junctional, Herlitz type, 226700 (3) to Epidermolysis bullosa, junctional 1A, intermediate MIM#226650; Epidermolysis bullosa, junctional 1B, severe MIM#226700
Prepair 1000+ v1.1647 LAMB3 Zornitza Stark Publications for gene: LAMB3 were set to
Prepair 1000+ v1.1646 LAMA3 Zornitza Stark Marked gene: LAMA3 as ready
Prepair 1000+ v1.1646 LAMA3 Zornitza Stark Gene: lama3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1646 LAMA3 Zornitza Stark Phenotypes for gene: LAMA3 were changed from Epidermolysis bullosa, junctional, Herlitz type, 226700 (3) to Epidermolysis bullosa, junctional 2B, severe (MIM#619784); 3. Epidermolysis bullosa, junctional 2C, laryngoonychocutaneous (MIM#245660); Epidermolysis bullosa, junctional 2A, intermediate (MIM#619783)
Prepair 1000+ v1.1645 LAMA3 Zornitza Stark Publications for gene: LAMA3 were set to
Prepair 1000+ v1.1644 LAMA1 Zornitza Stark Marked gene: LAMA1 as ready
Prepair 1000+ v1.1644 LAMA1 Zornitza Stark Gene: lama1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1644 LAMA1 Zornitza Stark Phenotypes for gene: LAMA1 were changed from Poretti-Boltshauser syndrome, 615960 (3) to Poretti-Boltshauser syndrome, MIM #615960
Prepair 1000+ v1.1643 LAMA1 Zornitza Stark Publications for gene: LAMA1 were set to
Prepair 1000+ v1.1642 KLHL40 Zornitza Stark Marked gene: KLHL40 as ready
Prepair 1000+ v1.1642 KLHL40 Zornitza Stark Gene: klhl40 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1642 KLHL40 Zornitza Stark Phenotypes for gene: KLHL40 were changed from Nemaline myopathy 8, autosomal recessive, 615348 (3) to Nemaline myopathy 8, autosomal recessive MIM#615348
Prepair 1000+ v1.1641 KLHL40 Zornitza Stark Publications for gene: KLHL40 were set to
Prepair 1000+ v1.1640 JAM3 Zornitza Stark Marked gene: JAM3 as ready
Prepair 1000+ v1.1640 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1640 JAM3 Zornitza Stark Phenotypes for gene: JAM3 were changed from Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, 613730 (3) to Haemorrhagic destruction of the brain, subependymal calcification, and cataracts MIM#613730
Prepair 1000+ v1.1639 JAM3 Zornitza Stark Publications for gene: JAM3 were set to
Prepair 1000+ v1.1638 IVD Zornitza Stark Marked gene: IVD as ready
Prepair 1000+ v1.1638 IVD Zornitza Stark Gene: ivd has been classified as Green List (High Evidence).
Prepair 1000+ v1.1638 IVD Zornitza Stark Phenotypes for gene: IVD were changed from Isovaleric acidemia, 243500 (3) to Isovaleric acidemia, MIM #243500
Prepair 1000+ v1.1637 IVD Zornitza Stark Publications for gene: IVD were set to
Prepair 1000+ v1.1636 IQCB1 Zornitza Stark Marked gene: IQCB1 as ready
Prepair 1000+ v1.1636 IQCB1 Zornitza Stark Gene: iqcb1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1636 IQCB1 Zornitza Stark Phenotypes for gene: IQCB1 were changed from Senior-Loken syndrome 5, 609254 (3) to Senior-Loken syndrome 5 MIM#609254
Prepair 1000+ v1.1635 IQCB1 Zornitza Stark Publications for gene: IQCB1 were set to
Prepair 1000+ v1.1634 INSR Zornitza Stark Marked gene: INSR as ready
Prepair 1000+ v1.1634 INSR Zornitza Stark Gene: insr has been classified as Green List (High Evidence).
Prepair 1000+ v1.1634 INSR Zornitza Stark Phenotypes for gene: INSR were changed from Leprechaunism, 246200 (3) to Donohue syndrome MIM#246200; Rabson-Mendenhall syndrome MIM#262190
Prepair 1000+ v1.1633 INSR Zornitza Stark Publications for gene: INSR were set to
Prepair 1000+ v1.1632 IFNGR1 Zornitza Stark Marked gene: IFNGR1 as ready
Prepair 1000+ v1.1632 IFNGR1 Zornitza Stark Gene: ifngr1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1632 IFNGR1 Zornitza Stark Phenotypes for gene: IFNGR1 were changed from Immunodeficiency 27A, mycobacteriosis, AR, 209950 (3) to Immunodeficiency 27A, mycobacteriosis, MIM#209950
Prepair 1000+ v1.1631 IFNGR1 Zornitza Stark Publications for gene: IFNGR1 were set to
Prepair 1000+ v1.1630 IER3IP1 Zornitza Stark Marked gene: IER3IP1 as ready
Prepair 1000+ v1.1630 IER3IP1 Zornitza Stark Gene: ier3ip1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1630 IER3IP1 Zornitza Stark Phenotypes for gene: IER3IP1 were changed from Microcephaly, epilepsy, and diabetes syndrome, 614231 (3) to Microcephaly, epilepsy, and diabetes syndrome, MIM# 614231
Prepair 1000+ v1.1629 HPD Zornitza Stark Marked gene: HPD as ready
Prepair 1000+ v1.1629 HPD Zornitza Stark Gene: hpd has been classified as Green List (High Evidence).
Prepair 1000+ v1.1629 HPD Zornitza Stark Phenotypes for gene: HPD were changed from Tyrosinemia, type III, 276710 (3) to Tyrosinemia, type III, MIM#276710
Prepair 1000+ v1.1628 HPD Zornitza Stark Publications for gene: HPD were set to
Prepair 1000+ v1.1627 HPD Zornitza Stark reviewed gene: HPD: Rating: GREEN; Mode of pathogenicity: None; Publications: 29456978; Phenotypes: Tyrosinemia, type III, MIM#276710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1627 HMGCL Zornitza Stark Marked gene: HMGCL as ready
Prepair 1000+ v1.1627 HMGCL Zornitza Stark Gene: hmgcl has been classified as Green List (High Evidence).
Prepair 1000+ v1.1627 HMGCL Zornitza Stark Phenotypes for gene: HMGCL were changed from HMG-CoA lyase deficiency, 246450 (3) to HMG-CoA lyase deficiency, MIM# 246450
Prepair 1000+ v1.1626 HBB Zornitza Stark Tag for review tag was added to gene: HBB.
Prepair 1000+ v1.1626 HADHA Zornitza Stark Marked gene: HADHA as ready
Prepair 1000+ v1.1626 HADHA Zornitza Stark Gene: hadha has been classified as Green List (High Evidence).
Prepair 1000+ v1.1626 HADHA Zornitza Stark Phenotypes for gene: HADHA were changed from Fatty liver, acute, of pregnancy, 609016 (3) to LCHAD deficiency MIM#609016; Mitochondrial trifunctional protein deficiency 1 MIM#609015
Prepair 1000+ v1.1625 GTPBP3 Zornitza Stark Marked gene: GTPBP3 as ready
Prepair 1000+ v1.1625 GTPBP3 Zornitza Stark Gene: gtpbp3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1625 GTPBP3 Zornitza Stark Phenotypes for gene: GTPBP3 were changed from Combined oxidative phosphorylation deficiency 23, 616198 (3) to Combined oxidative phosphorylation deficiency 23 MIM#616198
Prepair 1000+ v1.1624 GTPBP3 Zornitza Stark Publications for gene: GTPBP3 were set to
Prepair 1000+ v1.1623 GNPTG Zornitza Stark Marked gene: GNPTG as ready
Prepair 1000+ v1.1623 GNPTG Zornitza Stark Gene: gnptg has been classified as Green List (High Evidence).
Prepair 1000+ v1.1623 GNPTG Zornitza Stark Phenotypes for gene: GNPTG were changed from Mucolipidosis III gamma, 252605 (3) to Mucolipidosis III gamma, MIM# 252605
Prepair 1000+ v1.1622 GNPTG Zornitza Stark Publications for gene: GNPTG were set to
Prepair 1000+ v1.1621 GLE1 Zornitza Stark Marked gene: GLE1 as ready
Prepair 1000+ v1.1621 GLE1 Zornitza Stark Gene: gle1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1621 GLE1 Zornitza Stark Phenotypes for gene: GLE1 were changed from Arthrogryposis, lethal, with anterior horn cell disease, 611890 (3) to Congenital arthrogryposis with anterior horn cell disease, MIM #611890; Lethal congenital contracture syndrome 1, MIM #253310
Prepair 1000+ v1.1620 GLE1 Zornitza Stark Publications for gene: GLE1 were set to
Prepair 1000+ v1.1619 GDI1 Zornitza Stark Marked gene: GDI1 as ready
Prepair 1000+ v1.1619 GDI1 Zornitza Stark Gene: gdi1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1619 GDI1 Zornitza Stark Phenotypes for gene: GDI1 were changed from Mental retardation, X-linked 41, 300849 (3) to Intellectual developmental disorder, X-linked 41, MIM #300849
Prepair 1000+ v1.1618 GDI1 Zornitza Stark Publications for gene: GDI1 were set to
Prepair 1000+ v1.1617 GDF1 Zornitza Stark Marked gene: GDF1 as ready
Prepair 1000+ v1.1617 GDF1 Zornitza Stark Gene: gdf1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1617 GDF1 Zornitza Stark Publications for gene: GDF1 were set to
Prepair 1000+ v1.1616 GDF1 Zornitza Stark Phenotypes for gene: GDF1 were changed from Right atrial isomerism, 208530 (3) to Congenital heart defects, multiple types, 6 MIM#613854; Right atrial isomerism (Ivemark), MIM #208530
Prepair 1000+ v1.1615 GDAP1 Zornitza Stark Marked gene: GDAP1 as ready
Prepair 1000+ v1.1615 GDAP1 Zornitza Stark Gene: gdap1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1615 GDAP1 Zornitza Stark Phenotypes for gene: GDAP1 were changed from Charcot-Marie-Tooth disease, recessive intermediate, A, 608340 (3) to Charcot-Marie-Tooth disease, axonal, type 2K, MIM #607831; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, MIM #607706; Charcot-Marie-Tooth disease, recessive intermediate, A, MIM #608340; Charcot-Marie-Tooth disease, type 4A, MIM#214400
Prepair 1000+ v1.1614 GDAP1 Zornitza Stark Publications for gene: GDAP1 were set to
Prepair 1000+ v1.1613 GAS8 Zornitza Stark Marked gene: GAS8 as ready
Prepair 1000+ v1.1613 GAS8 Zornitza Stark Gene: gas8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1613 GAS8 Zornitza Stark Phenotypes for gene: GAS8 were changed from Ciliary dyskinesia, primary, 33, 616726 (3), Autosomal recessive to Ciliary dyskinesia, primary, 33 MIM#616726
Prepair 1000+ v1.1612 GAS8 Zornitza Stark Publications for gene: GAS8 were set to
Regression v0.574 KLC4 Zornitza Stark gene: KLC4 was added
gene: KLC4 was added to Regression. Sources: Literature
Mode of inheritance for gene: KLC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLC4 were set to 26423925
Phenotypes for gene: KLC4 were set to Neurodegeneration, early-childhood-onset, with retinitis pigmentosa, sensorineural hearing loss, and demyelinating peripheral neuropathy, MIM# 621129
Review for gene: KLC4 was set to RED
Added comment: Single family reported with three affected sibs, homozygous variant.
Sources: Literature
Mendeliome v1.2386 KLC4 Zornitza Stark edited their review of gene: KLC4: Changed phenotypes: Neurodegeneration, early-childhood-onset, with retinitis pigmentosa, sensorineural hearing loss, and demyelinating peripheral neuropathy, MIM# 621129
Syndromic Retinopathy v0.221 EXOSC2 Zornitza Stark Publications for gene: EXOSC2 were set to 26843489; 31628467
Syndromic Retinopathy v0.220 EXOSC2 Zornitza Stark Classified gene: EXOSC2 as Amber List (moderate evidence)
Syndromic Retinopathy v0.220 EXOSC2 Zornitza Stark Gene: exosc2 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.219 EXOSC2 Zornitza Stark edited their review of gene: EXOSC2: Added comment: LIMITED by ClinGen. Two additional patients reported but again, predominantly missense variants.; Changed publications: 26843489, 31628467, 36344539, 36069504
Intellectual disability syndromic and non-syndromic v1.86 EXOSC2 Zornitza Stark Publications for gene: EXOSC2 were set to 26843489; 31628467
Intellectual disability syndromic and non-syndromic v1.85 EXOSC2 Zornitza Stark edited their review of gene: EXOSC2: Added comment: LIMITED by ClinGen. Two additional patients reported but again, predominantly missense variants.; Changed rating: AMBER; Changed publications: 26843489, 31628467, 36344539, 36069504
Mendeliome v1.2386 EXOSC2 Zornitza Stark changed review comment from: LIMITED by ClinGen; to: LIMITED by ClinGen. Two additional patients reported but again, predominantly missense variants.
Mendeliome v1.2386 EXOSC2 Zornitza Stark edited their review of gene: EXOSC2: Changed publications: 26843489, 31628467, 36344539, 36069504
Mendeliome v1.2386 EXOSC2 Zornitza Stark commented on gene: EXOSC2: LIMITED by ClinGen
Renal Macrocystic Disease v0.82 COL4A5 Zornitza Stark Classified gene: COL4A5 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.82 COL4A5 Zornitza Stark Gene: col4a5 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.81 COL4A5 Zornitza Stark reviewed gene: COL4A5: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Renal Macrocystic Disease v0.81 COL4A4 Zornitza Stark Classified gene: COL4A4 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.81 COL4A4 Zornitza Stark Gene: col4a4 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.80 COL4A4 Zornitza Stark reviewed gene: COL4A4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Macrocystic Disease v0.80 COL4A3 Zornitza Stark Classified gene: COL4A3 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.80 COL4A3 Zornitza Stark Gene: col4a3 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.79 COL4A3 Zornitza Stark reviewed gene: COL4A3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Alport syndrome MONDO:0018965; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2386 LSM1 Zornitza Stark Phenotypes for gene: LSM1 were changed from intellectual disability; congenital abnormalities to neurodevelopmental disorder MONDO:0700092, LSM1-related
Mendeliome v1.2385 LSM1 Sangavi Sivagnanasundram reviewed gene: LSM1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092; Mode of inheritance: None
Prepair 1000+ v1.1611 TTC21B Kate Scarff changed review comment from: Short-rib thoracic dysplasia (SRTD) with or without polydactyly is a skeletal ciliopathy characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present. Nonskeletal involvement can include cleft lip/palate as well as anomalies of the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life.
Homozygous null alleles in Ttc21b are embryonic lethal in mice and it is likely that biallelic truncating null variants are equally incompatible with survival in humans.

Nephronophthisis 12: End stage kidney disease seen in multiple unrelated children <10 years. Patients harboring one truncating or splice site mutation in addition to a missense variant exhibit JATD or early onset NPHP with extra-renal features, whereas patients carrying homozygous p.Pro209Leu variants display a primarily kidney phenotype with NPHP and often with glomerular involvement (FSGS). However, liver and skeletal involvement as well as high myopia have also been described in patients with biallelic missense variants, including homozygous p.Pro209Leu carriers.; to: Short-rib thoracic dysplasia (SRTD) with or without polydactyly is a skeletal ciliopathy characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present. Nonskeletal involvement can include cleft lip/palate as well as anomalies of the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life.
Homozygous null alleles in Ttc21b are embryonic lethal in mice and it is likely that biallelic truncating null variants are equally incompatible with survival in humans.

Nephronophthisis 12: End stage kidney disease seen in multiple unrelated children <10 years. Patients harboring one truncating or splice site mutation in addition to a missense variant exhibit SRTD or early onset NPHP with extra-renal features, whereas patients carrying homozygous p.Pro209Leu variants display a primarily kidney phenotype with NPHP and often with glomerular involvement (FSGS). However, liver and skeletal involvement as well as high myopia have also been described in patients with biallelic missense variants, including homozygous p.Pro209Leu carriers.
Prepair 1000+ v1.1611 TTC21B Kate Scarff edited their review of gene: TTC21B: Changed phenotypes: Short-rib thoracic dysplasia 4 with or without polydactyly, MIM #613819, Nephronophthisis 12, MIM #613820
Prepair 1000+ v1.1611 TTC21B Kate Scarff changed review comment from: Short-rib thoracic dysplasia (SRTD) with or without polydactyly is a skeletal ciliopathy characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present. Nonskeletal involvement can include cleft lip/palate as well as anomalies of the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life.
Homozygous null alleles in Ttc21b are embryonic lethal in mice and it is likely that biallelic truncating null variants are equally incompatible with survival in humans.; to: Short-rib thoracic dysplasia (SRTD) with or without polydactyly is a skeletal ciliopathy characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present. Nonskeletal involvement can include cleft lip/palate as well as anomalies of the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life.
Homozygous null alleles in Ttc21b are embryonic lethal in mice and it is likely that biallelic truncating null variants are equally incompatible with survival in humans.

Nephronophthisis 12: End stage kidney disease seen in multiple unrelated children <10 years. Patients harboring one truncating or splice site mutation in addition to a missense variant exhibit JATD or early onset NPHP with extra-renal features, whereas patients carrying homozygous p.Pro209Leu variants display a primarily kidney phenotype with NPHP and often with glomerular involvement (FSGS). However, liver and skeletal involvement as well as high myopia have also been described in patients with biallelic missense variants, including homozygous p.Pro209Leu carriers.
Prepair 1000+ v1.1611 TRIP11 Kate Scarff edited their review of gene: TRIP11: Changed phenotypes: Achondrogenesis, type IA, MIM #200600, Odontochondrodysplasia 1, MIM #184260
Mendeliome v1.2385 RP9 Sangavi Sivagnanasundram reviewed gene: RP9: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008710; Phenotypes: retinitis pigmentosa 9 MONDO:0008378; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Prepair 1000+ v1.1611 DBR1 Lilian Downie Marked gene: DBR1 as ready
Prepair 1000+ v1.1611 DBR1 Lilian Downie Added comment: Comment when marking as ready: Green for the immune condition in OMIM Xerosis and growth failure with immune and pulmonary dysfunction syndrome MIM#620510 although evidence is from a single paper but includes 4 unrelated families, 2 papers regarding encephalopathy, again enough evidence for inclusion >3 unrelated families.

UPGRADE TO GREEN
Prepair 1000+ v1.1611 DBR1 Lilian Downie Gene: dbr1 has been removed from the panel.
Prepair 1000+ v1.1611 AMN Lilian Downie Marked gene: AMN as ready
Prepair 1000+ v1.1611 AMN Lilian Downie Added comment: Comment when marking as ready: Treatable disorder with good outcomes
Prepair 1000+ v1.1611 AMN Lilian Downie Gene: amn has been removed from the panel.
Prepair 1000+ v1.1611 AMN Lilian Downie Publications for gene: AMN were set to
Prepair 1000+ v1.1610 ERCC5 Lilian Downie Marked gene: ERCC5 as ready
Prepair 1000+ v1.1610 ERCC5 Lilian Downie Gene: ercc5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1610 ERCC5 Lilian Downie Phenotypes for gene: ERCC5 were changed from Xeroderma pigmentosum, group G, 278780 (3) to Cerebrooculofacioskeletal syndrome 3, MIM# 616570; MONDO:0014696; Xeroderma pigmentosum, group G, MIM# 278780; MONDO:0010216
Prepair 1000+ v1.1609 ERCC5 Lilian Downie Publications for gene: ERCC5 were set to
Prepair 1000+ v1.1608 FAH Lilian Downie Marked gene: FAH as ready
Prepair 1000+ v1.1608 FAH Lilian Downie Gene: fah has been classified as Green List (High Evidence).
Prepair 1000+ v1.1608 FAH Lilian Downie Publications for gene: FAH were set to
Prepair 1000+ v1.1607 FAM126A Lilian Downie Marked gene: FAM126A as ready
Prepair 1000+ v1.1607 FAM126A Lilian Downie Gene: fam126a has been classified as Green List (High Evidence).
Prepair 1000+ v1.1607 FAM126A Lilian Downie Publications for gene: FAM126A were set to
Prepair 1000+ v1.1606 FANCA Lilian Downie Marked gene: FANCA as ready
Prepair 1000+ v1.1606 FANCA Lilian Downie Gene: fanca has been classified as Green List (High Evidence).
Prepair 1000+ v1.1606 FBP1 Lilian Downie Marked gene: FBP1 as ready
Prepair 1000+ v1.1606 FBP1 Lilian Downie Gene: fbp1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1606 FBP1 Lilian Downie Publications for gene: FBP1 were set to
Prepair 1000+ v1.1605 FERMT3 Lilian Downie Marked gene: FERMT3 as ready
Prepair 1000+ v1.1605 FERMT3 Lilian Downie Gene: fermt3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1605 FERMT3 Lilian Downie Publications for gene: FERMT3 were set to
Prepair 1000+ v1.1604 WRAP53 Lilian Downie Marked gene: WRAP53 as ready
Prepair 1000+ v1.1604 WRAP53 Lilian Downie Gene: wrap53 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1604 WRAP53 Lilian Downie Publications for gene: WRAP53 were set to
Prepair 1000+ v1.1603 XPC Lilian Downie Marked gene: XPC as ready
Prepair 1000+ v1.1603 XPC Lilian Downie Gene: xpc has been classified as Green List (High Evidence).
Prepair 1000+ v1.1603 XPC Lilian Downie Publications for gene: XPC were set to
Prepair 1000+ v1.1602 ZNF469 Lilian Downie Marked gene: ZNF469 as ready
Prepair 1000+ v1.1602 ZNF469 Lilian Downie Added comment: Comment when marking as ready: Upgrade to green
Prepair 1000+ v1.1602 ZNF469 Lilian Downie Gene: znf469 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.1602 ZNF469 Lilian Downie Publications for gene: ZNF469 were set to
Prepair 1000+ v1.1601 DHCR24 Lilian Downie Marked gene: DHCR24 as ready
Prepair 1000+ v1.1601 DHCR24 Lilian Downie Gene: dhcr24 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1601 DHCR24 Lilian Downie Publications for gene: DHCR24 were set to
Prepair 1000+ v1.1600 DNAAF4 Lilian Downie Marked gene: DNAAF4 as ready
Prepair 1000+ v1.1600 DNAAF4 Lilian Downie Added comment: Comment when marking as ready: Primary ciliary dyskinesia-25 is an autosomal recessive disorder caused by defective ciliary movement. Affected individuals have recurrent upper and lower airway disease, bronchiectasis, and decreased fertility. About half of patients show laterality defects, including situs inversus totalis.
Prepair 1000+ v1.1600 DNAAF4 Lilian Downie Gene: dnaaf4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1600 DNAAF4 Lilian Downie Tag cnv tag was added to gene: DNAAF4.
Prepair 1000+ v1.1600 DNAAF4 Lilian Downie Publications for gene: DNAAF4 were set to PMID: 20301301; 23872636
Prepair 1000+ v1.1599 DNAAF4 Lilian Downie Publications for gene: DNAAF4 were set to
Prepair 1000+ v1.1598 TRIP11 Kate Scarff changed review comment from: Characterized radiographically by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death. In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues.
Described in >10 unrelated families
Knockout mouse model PMID: 20089971
Deep intronic variants have been described PMID: 34057271, 34014608; to: ACG1A: Characterized radiographically by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death. In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues.
Described in >10 unrelated families
Knockout mouse model PMID: 20089971
Deep intronic variants have been described PMID: 34057271, 34014608

Odontochondrodysplasia 1: non-lethal skeletal dysplasia characterized by involvement of the spine and metaphyseal regions of the long bones, pulmonary hypoplasia, short stature, joint hypermobility, and dentinogenesis imperfecta. Variable severity.

Null mutations of TRIP11 lead to ACG1A, while splicing/hypomorphic mutations cause ODCD (PMID: 34111908, 30728324).
Prepair 1000+ v1.1598 TMEM107 Kate Scarff changed review comment from: Ciliopathy
26518474: one patient with bilateral postaxial polydactyly in hands and feet, multiple tongue cysts, and several facial dysmorphic features including frontal narrowing, short palpebral fissures, flat nasal bridge, retrognathia, and low-set ears. Mutation was del Phe106.
26595381: one patient with OFD had homozygous missense variant, another patient with Joubert syndrome comp het for del Phe106 and a frameshift deletion.
26123494: Meckel–Gruber syndrome cases in this paper were defined on the basis of occipital encephalocele, perinatal lethality and either polydactyly or polycystic kidneys. Two individuals had a homozygous p.Ser92Cysfs*7 variant were identified.

Unclear if we should also be reporting other phenotypes: ?Joubert syndrome 29/Meckel syndrome 13, MIM #617562; to: Ciliopathy
26518474: one patient with bilateral postaxial polydactyly in hands and feet, multiple tongue cysts, and several facial dysmorphic features including frontal narrowing, short palpebral fissures, flat nasal bridge, retrognathia, and low-set ears. Mutation was del Phe106.
26595381: one patient with OFD had homozygous missense variant, another patient with Joubert syndrome comp het for del Phe106 and a frameshift deletion.
26123494: Meckel–Gruber syndrome cases in this paper were defined on the basis of occipital encephalocele, perinatal lethality and either polydactyly or polycystic kidneys. Two individuals had a homozygous p.Ser92Cysfs*7 variant identified.

OMIM denotes with a ? that for Joubert syndrome 29, MIM #617562, it indicates that the relationship between the phenotype and gene is provisional.
Prepair 1000+ v1.1598 TMEM107 Kate Scarff edited their review of gene: TMEM107: Changed phenotypes: Orofaciodigital syndrome XVI, MIM #617563, Meckel syndrome 13, MIM #617562, ?Joubert syndrome 29, MIM #617562
Congenital Heart Defect v0.434 NFE2L2 Zornitza Stark Marked gene: NFE2L2 as ready
Congenital Heart Defect v0.434 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.434 NFE2L2 Zornitza Stark Classified gene: NFE2L2 as Amber List (moderate evidence)
Congenital Heart Defect v0.434 NFE2L2 Zornitza Stark Gene: nfe2l2 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.433 NFE2L2 Zornitza Stark gene: NFE2L2 was added
gene: NFE2L2 was added to Congenital Heart Defect. Sources: Expert Review
Mode of inheritance for gene: NFE2L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFE2L2 were set to 29018201
Phenotypes for gene: NFE2L2 were set to Immunodeficiency, developmental delay, and hypohomocysteinemia, MIM# 617744
Review for gene: NFE2L2 was set to AMBER
Added comment: CHD in two of the four affected individuals reported in the literature.
Sources: Expert Review
Genetic Epilepsy v1.120 KMT2C Zornitza Stark Phenotypes for gene: KMT2C were changed from Kleefstra syndrome 2, MIM# 617768 to Kleefstra syndrome 2, MIM# 617768; Neurodevelopmental disorder, MONDO:0700092, KMT2C-related
Genetic Epilepsy v1.119 KMT2C Zornitza Stark edited their review of gene: KMT2C: Added comment: Features not typical of Kleefstra syndrome and suggestion to rename condition to a broader NDD.; Changed phenotypes: Kleefstra syndrome 2, MIM# 617768, Neurodevelopmental disorder, MONDO:0700092, KMT2C-related
Intellectual disability syndromic and non-syndromic v1.85 KMT2C Zornitza Stark Phenotypes for gene: KMT2C were changed from Kleefstra syndrome 2, MIM#617768 to Kleefstra syndrome 2, MIM#617768; Neurodevelopmental disorder, MONDO:0700092, KMT2C-related
Intellectual disability syndromic and non-syndromic v1.84 KMT2C Zornitza Stark Publications for gene: KMT2C were set to
Intellectual disability syndromic and non-syndromic v1.83 KMT2C Zornitza Stark edited their review of gene: KMT2C: Added comment: Additional report of >80 individuals suggesting condition is distinct from Kleefstra syndrome and needs to be renamed.; Changed publications: 39013459; Changed phenotypes: Kleefstra syndrome 2, MIM#617768, Neurodevelopmental disorder, MONDO:0700092, KMT2C-related
Mendeliome v1.2385 KMT2C Zornitza Stark Publications for gene: KMT2C were set to
Mendeliome v1.2384 KMT2C Zornitza Stark Phenotypes for gene: KMT2C were changed from Kleefstra syndrome 2, MIM#617768 to Kleefstra syndrome 2, MIM#617768; Neurodevelopmental disorder, MONDO:0700092, KMT2C-related
Mendeliome v1.2383 KMT2C Zornitza Stark reviewed gene: KMT2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 39013459; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, KMT2C-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.1598 AHI1 Zornitza Stark Phenotypes for gene: AHI1 were changed from Joubert syndrome 3 MIM#608629 to Joubert syndrome 3 MIM#608629; Retinitis pigmentosa
Prepair 1000+ v1.1597 AHI1 Zornitza Stark Publications for gene: AHI1 were set to 16155189; 20301500
Prepair 1000+ v1.1596 AHI1 Zornitza Stark reviewed gene: AHI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28442542; Phenotypes: Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1596 XPNPEP3 Zornitza Stark Marked gene: XPNPEP3 as ready
Prepair 1000+ v1.1596 XPNPEP3 Zornitza Stark Added comment: Comment when marking as ready: For upgrade Green.
Prepair 1000+ v1.1596 XPNPEP3 Zornitza Stark Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.1596 XPNPEP3 Zornitza Stark Tag for review tag was added to gene: XPNPEP3.
Prepair 1000+ v1.1596 TTN Zornitza Stark Tag for review tag was added to gene: TTN.
Prepair 1000+ v1.1596 RP2 Kate Scarff changed review comment from: RP involves progressive retinal degeneration, symptoms include night blindness, development of tunnel vision, and slowly progressive decreased central vision.; to: RP involves progressive retinal degeneration, symptoms include night blindness, development of tunnel vision, and slowly progressive decreased central vision. Onset usually in first decade of life.
Prepair 1000+ v1.1596 RAB39B Kate Scarff changed review comment from: Characterised by intellectual disability with additional clinical features ranging from ASD, macrocephaly, seizures and/or early-onset parkinsonism.
One family had ~45kb deletion encompassing RAB39B gene and the last three coding exons of CLIC2 (PMID 25434005).

Unsure if Waisman syndrome 311510 is a distinct phenotype that should be reported, causes ID and Parkinson's (some juvenile PD).; to: Intellectual developmental disorder, X-linked 72; Characterised by intellectual disability with additional clinical features ranging from ASD, macrocephaly, seizures and/or early-onset parkinsonism.
One family had ~45kb deletion encompassing RAB39B gene and the last three coding exons of CLIC2 (PMID 25434005).

Waisman syndrome: neurologic disorder characterized by delayed psychomotor development, impaired intellectual development, and early-onset Parkinson disease (some juvenile PD).
Prepair 1000+ v1.1596 RAB39B Kate Scarff edited their review of gene: RAB39B: Changed phenotypes: Intellectual developmental disorder, X-linked 72, MIM #300271, Waisman syndrome, MIM #311510
Prepair 1000+ v1.1596 PSAP Kate Scarff edited their review of gene: PSAP: Changed phenotypes: Metachromatic leukodystrophy due to SAP-b deficiency, MIM #249900, Combined SAP deficiency, MIM #611721, Gaucher disease, atypical, MIM #610539, Krabbe disease, atypical, MIM #611722
Prepair 1000+ v1.1596 PEX1 Kate Scarff changed review comment from: Characterized clinically by severe neurologic dysfunction, craniofacial abnormalities, and liver dysfunction, and biochemically by the absence of peroxisomes. Most severely affected individuals with classic Zellweger syndrome phenotype die within the first year of life.
~98% of variants detectable by sequencing. The PEX1 variants c.2097_2098insT/p.Ile700YfsX42 and c.2528GRA/p.Gly843Asp are the most common.
Homozygosity for p.Ile700TyrfsTer42 is associated with a more severe phenotype. Homozygosity for p.Gly843Asp has to date been associated with a milder ZSD phenotype and sometimes with an intermediate phenotype.

Other phenotypes:
Peroxisome biogenesis disorder 1B (NALD/IRD), MIM #601539, characterised by overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), which represent the milder manifestations of the Zellweger syndrome spectrum. Many children presenting as newborns, whereas others do not come to attention until later. Many can communicate, and although language is rare, there have been children who have near normal language for age. Craniofacial anomalies are similar to but less pronounced than in Zellweger syndrome. In some individuals a leukodystrophy develops, with degeneration of myelin, loss of previously acquired skills, and development of spasticity; this may stabilize, or progress and be fatal. Associated with p.Gly843Asp variant?

Heimler syndrome-1 (MIM #234580) represents the mildest end of the peroxisomal biogenesis disorder spectrum, characterized by sensorineural hearing loss, enamel hypoplasia of the secondary dentition, and nail abnormalities. Not severe enough to report for P1000? See PMID: 26387595.; to: Characterized clinically by severe neurologic dysfunction, craniofacial abnormalities, and liver dysfunction, and biochemically by the absence of peroxisomes. Most severely affected individuals with classic Zellweger syndrome phenotype die within the first year of life.
~98% of variants detectable by sequencing. The PEX1 variants c.2097_2098insT/p.Ile700YfsX42 and c.2528GRA/p.Gly843Asp are the most common.
Homozygosity for p.Ile700TyrfsTer42 is associated with a more severe phenotype. Homozygosity for p.Gly843Asp has to date been associated with a milder ZSD phenotype and sometimes with an intermediate phenotype.

Other phenotypes:
Peroxisome biogenesis disorder 1B (NALD/IRD), MIM #601539, characterised by overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), which represent the milder manifestations of the Zellweger syndrome spectrum. Many children presenting as newborns, whereas others do not come to attention until later. Many can communicate, and although language is rare, there have been children who have near normal language for age. Craniofacial anomalies are similar to but less pronounced than in Zellweger syndrome. In some individuals a leukodystrophy develops, with degeneration of myelin, loss of previously acquired skills, and development of spasticity; this may stabilize, or progress and be fatal. Associated with p.Gly843Asp variant?

Heimler syndrome-1 (MIM #234580) represents the mildest end of the peroxisomal biogenesis disorder spectrum, characterized by sensorineural hearing loss, enamel hypoplasia of the secondary dentition, and nail abnormalities. Not severe enough to report for P1000? See PMID: 26387595.

MONDO:0100259 - Any Zellweger spectrum disorder in which the cause of the disease is a mutation in the PEX1 gene.
Prepair 1000+ v1.1596 PEX1 Kate Scarff edited their review of gene: PEX1: Changed phenotypes: Peroxisome biogenesis disorder 1A (Zellweger), MIM #214100, Heimler syndrome 1, MIM #234580, Peroxisome biogenesis disorder 1B (NALD/IRD), MIM #601539, MONDO:0100259
Prepair 1000+ v1.1596 PEX1 Kate Scarff changed review comment from: Characterized clinically by severe neurologic dysfunction, craniofacial abnormalities, and liver dysfunction, and biochemically by the absence of peroxisomes. Most severely affected individuals with classic Zellweger syndrome phenotype die within the first year of life.
~98% of variants detectable by sequencing. The PEX1 variants c.2097_2098insT/p.Ile700YfsX42 and c.2528GRA/p.Gly843Asp are the most common.
Homozygosity for p.Ile700TyrfsTer42 is associated with a more severe phenotype. Homozygosity for p.Gly843Asp has to date been associated with a milder ZSD phenotype and sometimes with an intermediate phenotype.

Other phenotypes:
Peroxisome biogenesis disorder 1B (NALD/IRD), MIM #601539, characterised by overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), which represent the milder manifestations of the Zellweger syndrome spectrum. Many children presenting as newborns, whereas others do not come to attention until later. Many can communicate, and although language is rare, there have been children who have near normal language for age. Craniofacial anomalies are similar to but less pronounced than in Zellweger syndrome. In some individuals a leukodystrophy develops, with degeneration of myelin, loss of previously acquired skills, and development of spasticity; this may stabilize, or progress and be fatal. Associated with p.Gly843Asp variant? Should this phenotype be included for P1000?

Heimler syndrome-1 (MIM #234580) represents the mildest end of the peroxisomal biogenesis disorder spectrum, characterized by sensorineural hearing loss, enamel hypoplasia of the secondary dentition, and nail abnormalities. Not severe enough to report for P1000. See PMID: 26387595.; to: Characterized clinically by severe neurologic dysfunction, craniofacial abnormalities, and liver dysfunction, and biochemically by the absence of peroxisomes. Most severely affected individuals with classic Zellweger syndrome phenotype die within the first year of life.
~98% of variants detectable by sequencing. The PEX1 variants c.2097_2098insT/p.Ile700YfsX42 and c.2528GRA/p.Gly843Asp are the most common.
Homozygosity for p.Ile700TyrfsTer42 is associated with a more severe phenotype. Homozygosity for p.Gly843Asp has to date been associated with a milder ZSD phenotype and sometimes with an intermediate phenotype.

Other phenotypes:
Peroxisome biogenesis disorder 1B (NALD/IRD), MIM #601539, characterised by overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), which represent the milder manifestations of the Zellweger syndrome spectrum. Many children presenting as newborns, whereas others do not come to attention until later. Many can communicate, and although language is rare, there have been children who have near normal language for age. Craniofacial anomalies are similar to but less pronounced than in Zellweger syndrome. In some individuals a leukodystrophy develops, with degeneration of myelin, loss of previously acquired skills, and development of spasticity; this may stabilize, or progress and be fatal. Associated with p.Gly843Asp variant?

Heimler syndrome-1 (MIM #234580) represents the mildest end of the peroxisomal biogenesis disorder spectrum, characterized by sensorineural hearing loss, enamel hypoplasia of the secondary dentition, and nail abnormalities. Not severe enough to report for P1000? See PMID: 26387595.
Prepair 1000+ v1.1596 PEX1 Kate Scarff edited their review of gene: PEX1: Changed phenotypes: Peroxisome biogenesis disorder 1A (Zellweger), MIM #214100, Heimler syndrome 1, MIM #234580, Peroxisome biogenesis disorder 1B (NALD/IRD), MIM #601539
Prepair 1000+ v1.1596 LARGE1 Kate Scarff edited their review of gene: LARGE1: Changed phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, MIM #613154, Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 6, MIM #608840
Prepair 1000+ v1.1596 LARGE1 Kate Scarff changed review comment from: Condition includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), involves characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. Described in >4 unrelated families.
Intragenic deletions have been reported (PMID: 17436019), as has an intragenic insertion/deletion (PMID: 21248746)

Should other phenotype for this gene be included? Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, MIM #608840, causes muscle weakness, brain abnormalities, and intellectual disability but does not affect the eyes. Phenotype described in Mendeliome.; to: Muscular dystrophy with impaired intellectual development and structural brain abnormalities type A, 6, MIM #613154: Condition includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), involves characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. Described in >4 unrelated families.
Intragenic deletions have been reported (PMID: 17436019), as has an intragenic insertion/deletion (PMID: 21248746)

Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, MIM #608840:
causes muscle weakness, structural brain abnormalities, and intellectual disability.
Skeletal dysplasia v0.307 MYH3 Bryony Thompson Marked gene: MYH3 as ready
Skeletal dysplasia v0.307 MYH3 Bryony Thompson Gene: myh3 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.307 MYH3 Bryony Thompson Classified gene: MYH3 as Green List (high evidence)
Skeletal dysplasia v0.307 MYH3 Bryony Thompson Gene: myh3 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.306 MYH3 Bryony Thompson gene: MYH3 was added
gene: MYH3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: MYH3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYH3 were set to 16642020; 29805041
Phenotypes for gene: MYH3 were set to Arthrogryposis, distal, type 2A (Freeman-Sheldon) 193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall) 618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A 178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B 618469
Review for gene: MYH3 was set to GREEN
gene: MYH3 was marked as current diagnostic
Added comment: Skeletal dysplasias are part of the spectrum MYH3-related conditions.
Sources: Literature
Lipodystrophy_Lipoatrophy v1.19 SUPT7L Zornitza Stark Phenotypes for gene: SUPT7L were changed from lipodystrophy, MONDO:0006573, SUPT7L-related to Fischer-Zirnsak progeroid syndrome, MIM# 621130
Lipodystrophy_Lipoatrophy v1.18 SUPT7L Zornitza Stark reviewed gene: SUPT7L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fischer-Zirnsak progeroid syndrome, MIM# 621130; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2383 SUPT7L Zornitza Stark Phenotypes for gene: SUPT7L were changed from Lipodystrophy, MONDO:0006573, SUPT7L-related to Fischer-Zirnsak progeroid syndrome, MIM# 621130
Mendeliome v1.2382 SUPT7L Zornitza Stark reviewed gene: SUPT7L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fischer-Zirnsak progeroid syndrome, MIM# 621130; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.316 CTGF Zornitza Stark Marked gene: CTGF as ready
Fetal anomalies v1.316 CTGF Zornitza Stark Gene: ctgf has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.316 CTGF Zornitza Stark Classified gene: CTGF as Amber List (moderate evidence)
Fetal anomalies v1.316 CTGF Zornitza Stark Gene: ctgf has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.315 CTGF Zornitza Stark gene: CTGF was added
gene: CTGF was added to Fetal anomalies. Sources: Literature
new gene name tags were added to gene: CTGF.
Mode of inheritance for gene: CTGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTGF were set to 39506047
Phenotypes for gene: CTGF were set to Kyphomelic dysplasia
Review for gene: CTGF was set to AMBER
Added comment: CCN2 is the new HGNC approved name.

PMID: 39506047
Three individuals from two unrelated consanguineous families presented with short stature, facial dysmorphism and kyphomelic skeletal dysplasia.

A rare missense variant in family 1 (Cys148Tyr) and novel frameshift variant (Pro260LeufsTer7) in family 2 was identified in homozygous state.
Zebrafish model was also conducted that showed altered body curvature and impaired cartilage formation in craniofacial region resulting in either bent or missing tails.

A missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5.
Sources: Literature
Prepair 1000+ v1.1596 DNAJC21 Lilian Downie Marked gene: DNAJC21 as ready
Prepair 1000+ v1.1596 DNAJC21 Lilian Downie Gene: dnajc21 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1596 DNAJC21 Lilian Downie Publications for gene: DNAJC21 were set to
Prepair 1000+ v1.1595 DNAJC6 Lilian Downie Marked gene: DNAJC6 as ready
Prepair 1000+ v1.1595 DNAJC6 Lilian Downie Gene: dnajc6 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1595 DNAJC6 Lilian Downie Publications for gene: DNAJC6 were set to
Prepair 1000+ v1.1594 DYNC2H1 Lilian Downie Marked gene: DYNC2H1 as ready
Prepair 1000+ v1.1594 DYNC2H1 Lilian Downie Gene: dync2h1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1594 DYNC2H1 Lilian Downie Publications for gene: DYNC2H1 were set to
Prepair 1000+ v1.1593 EIF2AK4 Lilian Downie Marked gene: EIF2AK4 as ready
Prepair 1000+ v1.1593 EIF2AK4 Lilian Downie Added comment: Comment when marking as ready: Downgrade to orange, onset is usually not until adulthood, teenage onset reported but usually 20's or later
Prepair 1000+ v1.1593 EIF2AK4 Lilian Downie Gene: eif2ak4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1593 EIF2AK4 Lilian Downie Publications for gene: EIF2AK4 were set to
Prepair 1000+ v1.1592 GAA Lilian Downie Marked gene: GAA as ready
Prepair 1000+ v1.1592 GAA Lilian Downie Gene: gaa has been classified as Green List (High Evidence).
Prepair 1000+ v1.1592 GAA Lilian Downie Phenotypes for gene: GAA were changed from Glycogen storage disease II, 232300 (3) to Glycogen storage disease II (Pompe disease), 232300
Prepair 1000+ v1.1591 GAA Lilian Downie Publications for gene: GAA were set to
Prepair 1000+ v1.1590 GJC2 Lilian Downie Marked gene: GJC2 as ready
Prepair 1000+ v1.1590 GJC2 Lilian Downie Gene: gjc2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1590 GJC2 Lilian Downie Publications for gene: GJC2 were set to
Prepair 1000+ v1.1589 GPR179 Lilian Downie Marked gene: GPR179 as ready
Prepair 1000+ v1.1589 GPR179 Lilian Downie Added comment: Comment when marking as ready: Orange or red at time of review, phenotype is not severe, non progressive visual impairment in low light only.
Prepair 1000+ v1.1589 GPR179 Lilian Downie Gene: gpr179 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1589 GPR179 Lilian Downie Phenotypes for gene: GPR179 were changed from Night blindness, congenital stationary (complete), 1E, autosomal recessive, 614565 (3) to GPR179-related retinopathy (MONDO:0800396)
Prepair 1000+ v1.1588 GPR179 Lilian Downie Publications for gene: GPR179 were set to
Prepair 1000+ v1.1587 GUCY2C Lilian Downie Marked gene: GUCY2C as ready
Prepair 1000+ v1.1587 GUCY2C Lilian Downie Added comment: Comment when marking as ready: Suggest demoting to orange or red, phenotype is not severe - requires early surgical management and then results in normal growth and development
Prepair 1000+ v1.1587 GUCY2C Lilian Downie Gene: gucy2c has been classified as Green List (High Evidence).
Prepair 1000+ v1.1587 GUCY2C Lilian Downie Publications for gene: GUCY2C were set to
Congenital Heart Defect v0.432 DZIP1 Bryony Thompson Classified gene: DZIP1 as Amber List (moderate evidence)
Congenital Heart Defect v0.432 DZIP1 Bryony Thompson Gene: dzip1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.431 DZIP1 Bryony Thompson gene: DZIP1 was added
gene: DZIP1 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: DZIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DZIP1 were set to 33811421; 31118289
Phenotypes for gene: DZIP1 were set to mitral valve prolapse MONDO:0004910
Review for gene: DZIP1 was set to AMBER
Added comment: Two unrelated families segregating 2 different missense variants (S24R - 53 hets and C585W - 12,414 alleles & 74 homs in gnomAD v4.1) with mitral valve prolapse. 2 rare missense (Pro47Leu - 10 hets & Arg267Ile - 118 hets in gnomAD v) identified in 2 unrelated sporadic MVP cases. Supporting mouse model of S24R impaired ciliogenesis during development, which progressed to adult myxomatous valve disease and functional MVP.
Sources: Literature
Mendeliome v1.2382 DZIP1 Bryony Thompson reviewed gene: DZIP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33811421, 31118289; Phenotypes: mitral valve prolapse MONDO:0004910; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2382 DYNC1H1 Bryony Thompson Publications for gene: DYNC1H1 were set to 25512093; 28196890
Mendeliome v1.2381 DYNC1H1 Bryony Thompson Phenotypes for gene: DYNC1H1 were changed from Charcot-Marie-Tooth disease, axonal, type 20; Mental retardation, autosomal dominant 13; Spinal muscular atrophy, lower extremity-predominant 1 to dyneinopathy MONDO:1040031
Mendeliome v1.2380 DUOXA2 Bryony Thompson Publications for gene: DUOXA2 were set to
Mendeliome v1.2379 DUOXA2 Bryony Thompson Mode of inheritance for gene: DUOXA2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2378 DUOXA1 Bryony Thompson Phenotypes for gene: DUOXA1 were changed from congenital hypothyroidism, No OMIM # to congenital hypothyroidism MONDO:0018612
Mendeliome v1.2377 DUOXA1 Bryony Thompson Publications for gene: DUOXA1 were set to 29650690
Mendeliome v1.2376 DUOXA1 Bryony Thompson Mode of inheritance for gene: DUOXA1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.2375 DUOX2 Bryony Thompson Added comment: Comment on mode of inheritance: Biallelic evidence for IBD is strong, but the evidence for the monoallelic association is limited. Semidominant inheritance for thyroid dyshormonogenesis.
Mendeliome v1.2375 DUOX2 Bryony Thompson Mode of inheritance for gene: DUOX2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.83 LINC01578 Zornitza Stark Tag non-coding gene tag was added to gene: LINC01578.
Mendeliome v1.2374 LINC01578 Zornitza Stark Tag non-coding gene tag was added to gene: LINC01578.
Susceptibility to Viral Infections v0.131 SNORA31 Zornitza Stark Tag non-coding gene tag was added to gene: SNORA31.
Defects of intrinsic and innate immunity v1.20 SNORA31 Zornitza Stark Marked gene: SNORA31 as ready
Defects of intrinsic and innate immunity v1.20 SNORA31 Zornitza Stark Gene: snora31 has been classified as Green List (High Evidence).
Defects of intrinsic and innate immunity v1.20 SNORA31 Zornitza Stark Tag non-coding gene tag was added to gene: SNORA31.
Mendeliome v1.2374 SNORA31 Zornitza Stark Tag non-coding gene tag was added to gene: SNORA31.
Deafness_Isolated v1.67 MIR96 Zornitza Stark Tag non-coding gene tag was added to gene: MIR96.
Deafness_IsolatedAndComplex v1.213 MIR96 Zornitza Stark Tag non-coding gene tag was added to gene: MIR96.
Mendeliome v1.2374 MIR96 Zornitza Stark Tag non-coding gene tag was added to gene: MIR96.
Mendeliome v1.2374 MIR936 Zornitza Stark Tag non-coding gene tag was added to gene: MIR936.
Mendeliome v1.2374 MIR5004 Zornitza Stark Tag non-coding gene tag was added to gene: MIR5004.
Cone-rod Dystrophy v0.54 MIR204 Zornitza Stark Tag non-coding gene tag was added to gene: MIR204.
Optic Atrophy v1.45 MIR204 Zornitza Stark Tag non-coding gene tag was added to gene: MIR204.
Mendeliome v1.2374 MIR204 Zornitza Stark Tag non-coding gene tag was added to gene: MIR204.
Mendeliome v1.2374 MIR184 Zornitza Stark Tag non-coding gene tag was added to gene: MIR184.
Cataract v0.373 MIR184 Zornitza Stark Tag non-coding gene tag was added to gene: MIR184.
Mendeliome v1.2374 MIR183 Zornitza Stark Tag non-coding gene tag was added to gene: MIR183.
Mendeliome v1.2374 MIR182 Zornitza Stark Tag non-coding gene tag was added to gene: MIR182.
Fetal anomalies v1.314 MIR17HG Zornitza Stark Tag non-coding gene tag was added to gene: MIR17HG.
Skeletal dysplasia v0.305 MIR17HG Zornitza Stark Tag non-coding gene tag was added to gene: MIR17HG.
Intellectual disability syndromic and non-syndromic v1.83 MIR17HG Zornitza Stark Tag non-coding gene tag was added to gene: MIR17HG.
Mendeliome v1.2374 MIR17HG Zornitza Stark Tag non-coding gene tag was added to gene: MIR17HG.
Gastrointestinal neuromuscular disease v1.24 MIR145 Zornitza Stark Tag non-coding gene tag was added to gene: MIR145.
Mendeliome v1.2374 MIR145 Zornitza Stark Tag non-coding gene tag was added to gene: MIR145.
Skeletal dysplasia v0.305 MIR140 Zornitza Stark Tag non-coding gene tag was added to gene: MIR140.
Mendeliome v1.2374 MIR140 Zornitza Stark Tag non-coding gene tag was added to gene: MIR140.
Fetal anomalies v1.314 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Prepair 1000+ v1.1586 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Genomic newborn screening: BabyScreen+ v1.116 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Hair disorders v0.71 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Metaphyseal dysplasias v0.5 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Ectodermal Dysplasia v0.89 RSPO4 Zornitza Stark Marked gene: RSPO4 as ready
Ectodermal Dysplasia v0.89 RSPO4 Zornitza Stark Gene: rspo4 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.89 RSPO4 Zornitza Stark Classified gene: RSPO4 as Green List (high evidence)
Ectodermal Dysplasia v0.89 RSPO4 Zornitza Stark Gene: rspo4 has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.88 RMRP Zornitza Stark Marked gene: RMRP as ready
Ectodermal Dysplasia v0.88 RMRP Zornitza Stark Gene: rmrp has been classified as Green List (High Evidence).
Ectodermal Dysplasia v0.88 RMRP Zornitza Stark Phenotypes for gene: RMRP were changed from Cartilage-hair hypoplasia, Metaphyseal dysplasia without hypotrichosis, Anauxetic dysplasia to Cartilage hair hypoplasia (CHH) MIM#250250; Anauxetic dysplasia 1, MIM# 607095; Metaphyseal dysplasia without hypotrichosis, MIM# 250460
Ectodermal Dysplasia v0.87 RMRP Zornitza Stark Publications for gene: RMRP were set to
Ectodermal Dysplasia v0.86 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Skeletal dysplasia v0.305 RMRP Zornitza Stark Marked gene: RMRP as ready
Skeletal dysplasia v0.305 RMRP Zornitza Stark Gene: rmrp has been classified as Green List (High Evidence).
Skeletal dysplasia v0.305 RMRP Zornitza Stark Publications for gene: RMRP were set to
Skeletal dysplasia v0.304 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Intellectual disability syndromic and non-syndromic v1.83 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Combined Immunodeficiency v1.115 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Mitochondrial disease v0.970 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Mendeliome v1.2374 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Bone Marrow Failure v1.114 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Skeletal Dysplasia_Fetal v0.230 RMRP Zornitza Stark Marked gene: RMRP as ready
Skeletal Dysplasia_Fetal v0.230 RMRP Zornitza Stark Gene: rmrp has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.230 RMRP Zornitza Stark Phenotypes for gene: RMRP were changed from to Anauxetic dysplasia 1, MIM#607095
Skeletal Dysplasia_Fetal v0.229 RMRP Zornitza Stark Mode of inheritance for gene: RMRP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.228 RMRP Zornitza Stark Tag non-coding gene tag was added to gene: RMRP.
Genomic newborn screening: BabyScreen+ v1.116 TERC Zornitza Stark Tag non-coding gene tag was added to gene: TERC.
IBMDx study v0.35 TERC Zornitza Stark Marked gene: TERC as ready
IBMDx study v0.35 TERC Zornitza Stark Gene: terc has been classified as Green List (High Evidence).
IBMDx study v0.35 TERC Zornitza Stark Phenotypes for gene: TERC were changed from Dyskeratosis congenita, autosomal dominant 1, MIM# 127550 to Dyskeratosis congenita, autosomal dominant 1, MIM# 127550; Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 2, MIM# 614743
IBMDx study v0.34 TERC Zornitza Stark Mode of inheritance for gene: TERC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
IBMDx study v0.33 TERC Zornitza Stark Tag non-coding gene tag was added to gene: TERC.
Combined Immunodeficiency v1.115 TERC Zornitza Stark Tag non-coding gene tag was added to gene: TERC.
Pulmonary Fibrosis_Interstitial Lung Disease v0.87 TERC Zornitza Stark Marked gene: TERC as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.87 TERC Zornitza Stark Gene: terc has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.87 TERC Zornitza Stark Phenotypes for gene: TERC were changed from to Dyskeratosis congenita, autosomal dominant 1, MIM# 127550; Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 2, MIM# 614743
Pulmonary Fibrosis_Interstitial Lung Disease v0.86 TERC Zornitza Stark Publications for gene: TERC were set to
Pulmonary Fibrosis_Interstitial Lung Disease v0.85 TERC Zornitza Stark Mode of inheritance for gene: TERC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Fibrosis_Interstitial Lung Disease v0.84 TERC Zornitza Stark Tag non-coding gene tag was added to gene: TERC.
Pulmonary Fibrosis_Interstitial Lung Disease v0.84 TERC Zornitza Stark edited their review of gene: TERC: Changed phenotypes: Dyskeratosis congenita, autosomal dominant 1, MIM# 127550, Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 2, MIM# 614743
Mendeliome v1.2374 TERC Zornitza Stark Phenotypes for gene: TERC were changed from Dyskeratosis congenita, autosomal dominant 1, MIM# 127550 to Dyskeratosis congenita, autosomal dominant 1, MIM# 127550; Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 2, MIM# 614743
Mendeliome v1.2373 TERC Zornitza Stark Tag non-coding gene tag was added to gene: TERC.
Mendeliome v1.2373 TERC Zornitza Stark edited their review of gene: TERC: Changed phenotypes: Dyskeratosis congenita, autosomal dominant 1, MIM# 127550, Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 2, MIM# 614743
Bone Marrow Failure v1.114 TERC Zornitza Stark Phenotypes for gene: TERC were changed from Dyskeratosis congenita, autosomal dominant 1, MIM# 127550 to Dyskeratosis congenita, autosomal dominant 1, MIM# 127550; Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 2, MIM# 614743
Bone Marrow Failure v1.113 TERC Zornitza Stark Tag non-coding gene tag was added to gene: TERC.
Bone Marrow Failure v1.113 TERC Zornitza Stark edited their review of gene: TERC: Changed phenotypes: Dyskeratosis congenita, autosomal dominant 1, MIM# 127550, Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 2, MIM# 614743
Intellectual disability syndromic and non-syndromic v1.83 RNU2-2P Zornitza Stark Tag non-coding gene tag was added to gene: RNU2-2P.
Genetic Epilepsy v1.119 RNU2-2P Zornitza Stark Tag non-coding gene tag was added to gene: RNU2-2P.
Mendeliome v1.2373 RNU2-2P Zornitza Stark Tag non-coding gene tag was added to gene: RNU2-2P.
Prepair 1000+ v1.1586 SNORD118 Zornitza Stark Tag non-coding gene tag was added to gene: SNORD118.
Fetal anomalies v1.314 SNORD118 Zornitza Stark Tag non-coding gene tag was added to gene: SNORD118.
Leukodystrophy - adult onset v0.143 SNORD118 Zornitza Stark Tag non-coding gene tag was added to gene: SNORD118.
Leukodystrophy - paediatric v0.318 SNORD118 Zornitza Stark Tag non-coding gene tag was added to gene: SNORD118.
Dystonia - complex v0.272 SNORD118 Zornitza Stark Tag non-coding gene tag was added to gene: SNORD118.
Intellectual disability syndromic and non-syndromic v1.83 SNORD118 Zornitza Stark Tag non-coding gene tag was added to gene: SNORD118.
Genetic Epilepsy v1.119 SNORD118 Zornitza Stark Tag non-coding gene tag was added to gene: SNORD118.
Mendeliome v1.2373 SNORD118 Zornitza Stark Tag non-coding gene tag was added to gene: SNORD118.
Brain Calcification v1.99 SNORD118 Zornitza Stark Tag non-coding gene tag was added to gene: SNORD118.
Hereditary Spastic Paraplegia - paediatric v1.87 RNU7-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU7-1.
Dystonia - complex v0.272 RNU7-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU7-1.
Intellectual disability syndromic and non-syndromic v1.83 RNU7-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU7-1.
Autoinflammatory Disorders v2.3 RNU7-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU7-1.
Regression v0.573 RNU7-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU7-1.
Mendeliome v1.2373 RNU7-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU7-1.
Cerebral Palsy v1.389 RNU7-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU7-1.
Brain Calcification v1.99 RNU7-1 Zornitza Stark Tag non-coding gene tag was added to gene: RNU7-1.
Fetal anomalies v1.314 RNU4ATAC Zornitza Stark Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I, MIM#210710; Roifman syndrome, MIM#616651 to RNU4ATAC spectrum disorder MONDO:0100558; Microcephalic osteodysplastic primordial dwarfism, type I, MIM#210710; Roifman syndrome, MIM#616651
Fetal anomalies v1.313 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Mendeliome v1.2373 RNU4ATAC Zornitza Stark Phenotypes for gene: RNU4ATAC were changed from Microcephalic osteodysplastic primordial dwarfism, type I (MIM# 210710); Roifman syndrome (MIM# 616651); Lowry-Wood syndrome, MIM# 226960 to RNU4ATAC spectrum disorder MONDO:0100558; Microcephalic osteodysplastic primordial dwarfism, type I (MIM# 210710); Roifman syndrome (MIM# 616651); Lowry-Wood syndrome, MIM# 226960
Prepair 1000+ v1.1586 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Growth failure v1.76 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Microcephalic Primordial Dwarfism and Slender bone dysplasias v0.29 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Syndromic Retinopathy v0.219 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Skeletal dysplasia v0.304 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Intellectual disability syndromic and non-syndromic v1.83 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Combined Immunodeficiency v1.115 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Callosome v0.540 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Genetic Epilepsy v1.119 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Microcephaly v1.301 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Mendeliome v1.2372 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Skeletal Dysplasia_Fetal v0.228 RNU4ATAC Zornitza Stark Marked gene: RNU4ATAC as ready
Skeletal Dysplasia_Fetal v0.228 RNU4ATAC Zornitza Stark Gene: rnu4atac has been classified as Green List (High Evidence).
Skeletal Dysplasia_Fetal v0.228 RNU4ATAC Zornitza Stark Phenotypes for gene: RNU4ATAC were changed from to Microcephalic osteodysplastic primordial dwarfism, type I, MIM#210710; Roifman syndrome, MIM#616651
Skeletal Dysplasia_Fetal v0.227 RNU4ATAC Zornitza Stark Mode of pathogenicity for gene: RNU4ATAC was changed from to Other
Skeletal Dysplasia_Fetal v0.226 RNU4ATAC Zornitza Stark Mode of inheritance for gene: RNU4ATAC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal Dysplasia_Fetal v0.225 RNU4ATAC Zornitza Stark Tag non-coding gene tag was added to gene: RNU4ATAC.
Intellectual disability syndromic and non-syndromic v1.83 RNU4-2 Zornitza Stark Tag non-coding gene tag was added to gene: RNU4-2.
Mendeliome v1.2372 RNU4-2 Zornitza Stark Tag non-coding gene tag was added to gene: RNU4-2.
Fetal anomalies v1.313 RNU12 Zornitza Stark Tag non-coding gene tag was added to gene: RNU12.
Mendeliome v1.2372 RNU12 Zornitza Stark Tag non-coding gene tag was added to gene: RNU12.
Craniosynostosis v1.68 RNU12 Zornitza Stark Tag non-coding gene tag was added to gene: RNU12.
Intellectual disability syndromic and non-syndromic v1.83 DROSHA Zornitza Stark Tag non-coding gene tag was added to gene: DROSHA.
Genetic Epilepsy v1.119 DROSHA Zornitza Stark Tag non-coding gene tag was added to gene: DROSHA.
Microcephaly v1.301 DROSHA Zornitza Stark Tag non-coding gene tag was added to gene: DROSHA.
Mendeliome v1.2372 DROSHA Zornitza Stark Tag non-coding gene tag was added to gene: DROSHA.
Skeletal dysplasia v0.304 MEG3 Zornitza Stark Marked gene: MEG3 as ready
Skeletal dysplasia v0.304 MEG3 Zornitza Stark Gene: meg3 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.304 MEG3 Zornitza Stark Classified gene: MEG3 as Green List (high evidence)
Skeletal dysplasia v0.304 MEG3 Zornitza Stark Gene: meg3 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.303 MEG3 Zornitza Stark gene: MEG3 was added
gene: MEG3 was added to Skeletal dysplasia. Sources: Expert list
SV/CNV, non-coding gene tags were added to gene: MEG3.
Mode of inheritance for gene: MEG3 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: MEG3 were set to 33010492; 33746039; 33067531; 38212313
Phenotypes for gene: MEG3 were set to Kagami-Ogata syndrome, MIM# 608149
Review for gene: MEG3 was set to GREEN
Added comment: Small deletions of MAG3 reported in multiple patients as one of the mechanisms of disease. Bell-shaped thorax and multiple other skeletal anomalies are a feature.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v1.83 MEG3 Zornitza Stark Marked gene: MEG3 as ready
Intellectual disability syndromic and non-syndromic v1.83 MEG3 Zornitza Stark Gene: meg3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.83 MEG3 Zornitza Stark Classified gene: MEG3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.83 MEG3 Zornitza Stark Gene: meg3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.82 MEG3 Zornitza Stark gene: MEG3 was added
gene: MEG3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: MEG3 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: MEG3 were set to 33010492; 33746039; 33067531; 38212313
Phenotypes for gene: MEG3 were set to Kagami-Ogata syndrome, MIM# 608149
Review for gene: MEG3 was set to GREEN
Added comment: Small deletions of MAG3 reported in multiple patients as one of the mechanisms of disease.
Sources: Expert list
Mendeliome v1.2372 MEG3 Zornitza Stark Marked gene: MEG3 as ready
Mendeliome v1.2372 MEG3 Zornitza Stark Gene: meg3 has been classified as Green List (High Evidence).
Mendeliome v1.2372 MEG3 Zornitza Stark Classified gene: MEG3 as Green List (high evidence)
Mendeliome v1.2372 MEG3 Zornitza Stark Gene: meg3 has been classified as Green List (High Evidence).
Mendeliome v1.2371 MEG3 Zornitza Stark gene: MEG3 was added
gene: MEG3 was added to Mendeliome. Sources: Literature
SV/CNV, non-coding gene tags were added to gene: MEG3.
Mode of inheritance for gene: MEG3 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: MEG3 were set to 33010492; 33746039; 33067531; 38212313
Phenotypes for gene: MEG3 were set to Kagami-Ogata syndrome, MIM# 608149
Review for gene: MEG3 was set to GREEN
Added comment: Small deletions of MAG3 reported in multiple patients as one of the mechanisms of disease.
Sources: Literature
Imprinting disorders v1.5 MEG3 Zornitza Stark Marked gene: MEG3 as ready
Imprinting disorders v1.5 MEG3 Zornitza Stark Gene: meg3 has been classified as Green List (High Evidence).
Imprinting disorders v1.5 MEG3 Zornitza Stark Tag SV/CNV tag was added to gene: MEG3.
Imprinting disorders v1.5 MEG3 Zornitza Stark Classified gene: MEG3 as Green List (high evidence)
Imprinting disorders v1.5 MEG3 Zornitza Stark Gene: meg3 has been classified as Green List (High Evidence).
Imprinting disorders v1.4 MEG3 Zornitza Stark gene: MEG3 was added
gene: MEG3 was added to Imprinting disorders. Sources: Expert list
non-coding gene tags were added to gene: MEG3.
Mode of inheritance for gene: MEG3 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: MEG3 were set to 33010492; 33746039; 33067531; 38212313
Phenotypes for gene: MEG3 were set to Kagami-Ogata syndrome, MIM# 608149
Review for gene: MEG3 was set to GREEN
Added comment: Small deletions of MAG3 reported in multiple patients as one of the mechanisms of disease.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v1.116 H19 Zornitza Stark Tag non-coding gene tag was added to gene: H19.
Fetal anomalies v1.313 H19 Zornitza Stark Tag non-coding gene tag was added to gene: H19.
Imprinting disorders v1.3 H19 Zornitza Stark Tag non-coding gene tag was added to gene: H19.
Growth failure v1.76 H19 Zornitza Stark Tag non-coding gene tag was added to gene: H19.
Additional findings_Paediatric v0.278 H19 Zornitza Stark Tag non-coding gene tag was added to gene: H19.
Intellectual disability syndromic and non-syndromic v1.81 H19 Zornitza Stark Tag non-coding gene tag was added to gene: H19.
Mendeliome v1.2370 H19 Zornitza Stark Tag non-coding gene tag was added to gene: H19.
Mendeliome v1.2370 CFAP54 Zornitza Stark Classified gene: CFAP54 as Amber List (moderate evidence)
Mendeliome v1.2370 CFAP54 Zornitza Stark Gene: cfap54 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2369 CFAP54 Zornitza Stark edited their review of gene: CFAP54: Added comment: PMID 37725231: three probands from two families with PCD, supportive mouse models x2.; Changed rating: AMBER; Changed publications: 26224312, 36593121, 37725231; Changed phenotypes: Spermatogenic failure 98, MIM# 621124, HCiliary dyskinesia, primary, 54, MIM# 621125
Ciliary Dyskinesia v1.47 CFAP54 Zornitza Stark Phenotypes for gene: CFAP54 were changed from Spermatogenic failure 98, MIM# 621124; Hydrocephalus, male infertility, mucus accumulation to Spermatogenic failure 98, MIM# 621124; Ciliary dyskinesia, primary, 54, MIM# 621125
Ciliary Dyskinesia v1.46 CFAP54 Zornitza Stark Publications for gene: CFAP54 were set to PMID: 26224312; 36593121
Ciliary Dyskinesia v1.45 CFAP54 Zornitza Stark Classified gene: CFAP54 as Amber List (moderate evidence)
Ciliary Dyskinesia v1.45 CFAP54 Zornitza Stark Gene: cfap54 has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v1.44 CFAP54 Zornitza Stark edited their review of gene: CFAP54: Added comment: PMID 37725231: three probands from two families with PCD, supportive mouse models x2.; Changed rating: AMBER; Changed publications: 36593121, 37725231; Changed phenotypes: Spermatogenic failure 98, MIM# 621124, Ciliary dyskinesia, primary, 54, MIM# 621125
Intellectual disability syndromic and non-syndromic v1.81 PPFIA3 Zornitza Stark Phenotypes for gene: PPFIA3 were changed from Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related to Paul-Chao neurodevelopmental syndrome, MIM# 621122
Intellectual disability syndromic and non-syndromic v1.80 PPFIA3 Zornitza Stark edited their review of gene: PPFIA3: Changed phenotypes: Paul-Chao neurodevelopmental syndrome, MIM# 621122
Genetic Epilepsy v1.119 PPFIA3 Zornitza Stark Phenotypes for gene: PPFIA3 were changed from Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related to Paul-Chao neurodevelopmental syndrome, MIM# 621122
Genetic Epilepsy v1.118 PPFIA3 Zornitza Stark edited their review of gene: PPFIA3: Changed phenotypes: Paul-Chao neurodevelopmental syndrome, MIM# 621122
Mendeliome v1.2369 PPFIA3 Zornitza Stark Phenotypes for gene: PPFIA3 were changed from Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related to Paul-Chao neurodevelopmental syndrome, MIM# 621122
Mendeliome v1.2368 PPFIA3 Zornitza Stark edited their review of gene: PPFIA3: Changed phenotypes: Paul-Chao neurodevelopmental syndrome, MIM# 621122
Prepair 1000+ v1.1586 ZNF335 Lauren Thomas reviewed gene: ZNF335: Rating: GREEN; Mode of pathogenicity: None; Publications: 38549403, 27540107, 29652087, 34982360; Phenotypes: Microcephaly 10, primary, autosomal recessive, MIM# 615095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1586 XPNPEP3 Lauren Thomas reviewed gene: XPNPEP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20179356, 32660933; Phenotypes: Nephronophthisis-like nephropathy 1, MIM# 613159; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1586 WDR73 Lauren Thomas reviewed gene: WDR73: Rating: GREEN; Mode of pathogenicity: None; Publications: 25466283, 26123727, 25873735, 26070982, 30315938; Phenotypes: Galloway-Mowat syndrome 1, MIM# 251300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1586 VPS13B Lauren Thomas reviewed gene: VPS13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 37692084, 19533689, 29758347, 19006247; Phenotypes: Cohen syndrome, MIM# 216550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1586 HEXA Lilian Downie Marked gene: HEXA as ready
Prepair 1000+ v1.1586 HEXA Lilian Downie Gene: hexa has been classified as Green List (High Evidence).
Prepair 1000+ v1.1586 HEXA Lilian Downie Publications for gene: HEXA were set to
Prepair 1000+ v1.1585 HMGCS2 Lilian Downie Marked gene: HMGCS2 as ready
Prepair 1000+ v1.1585 HMGCS2 Lilian Downie Gene: hmgcs2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1585 HMGCS2 Lilian Downie Publications for gene: HMGCS2 were set to
Prepair 1000+ v1.1584 HOGA1 Lilian Downie Publications for gene: HOGA1 were set to 31123811
Prepair 1000+ v1.1583 IGF1R Lilian Downie Marked gene: IGF1R as ready
Prepair 1000+ v1.1583 IGF1R Lilian Downie Gene: igf1r has been classified as Green List (High Evidence).
Prepair 1000+ v1.1583 IGF1R Lilian Downie Publications for gene: IGF1R were set to
Prepair 1000+ v1.1582 IQSEC2 Lilian Downie Marked gene: IQSEC2 as ready
Prepair 1000+ v1.1582 IQSEC2 Lilian Downie Gene: iqsec2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1582 IQSEC2 Lilian Downie Publications for gene: IQSEC2 were set to
Prepair 1000+ v1.1581 KDM5C Lilian Downie Marked gene: KDM5C as ready
Prepair 1000+ v1.1581 KDM5C Lilian Downie Gene: kdm5c has been classified as Green List (High Evidence).
Prepair 1000+ v1.1581 KDM5C Lilian Downie Publications for gene: KDM5C were set to
Prepair 1000+ v1.1580 L1CAM Lilian Downie Marked gene: L1CAM as ready
Prepair 1000+ v1.1580 L1CAM Lilian Downie Gene: l1cam has been classified as Green List (High Evidence).
Prepair 1000+ v1.1580 L1CAM Lilian Downie Phenotypes for gene: L1CAM were changed from MASA syndrome, 303350 (3) to MASA syndrome, MIM#303350; Hydrocephalus, congenital, X-linked, MIM#307000
Prepair 1000+ v1.1579 L1CAM Lilian Downie Publications for gene: L1CAM were set to
Prepair 1000+ v1.1578 LIFR Lilian Downie Marked gene: LIFR as ready
Prepair 1000+ v1.1578 LIFR Lilian Downie Gene: lifr has been classified as Green List (High Evidence).
Prepair 1000+ v1.1578 LIFR Lilian Downie Publications for gene: LIFR were set to
Prepair 1000+ v1.1577 ITGA6 Lauren Rogers reviewed gene: ITGA6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa, junctional 6, with pyloric atresia (MIM#619817); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1577 IER3IP1 Lauren Rogers reviewed gene: IER3IP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly, epilepsy, and diabetes syndrome, MIM# 614231; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1577 HMGCL Lauren Rogers reviewed gene: HMGCL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: HMG-CoA lyase deficiency, MIM# 246450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1577 HBB Lauren Rogers reviewed gene: HBB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sickle cell anaemia, MIM# 603903; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1577 SAMD9 Andrew Coventry reviewed gene: SAMD9: Rating: AMBER; Mode of pathogenicity: None; Publications: 37830462; Phenotypes: MIRAGE syndrome (MIM#617053), Monosomy 7 myelodysplasia and leukemia syndrome 2 (MIM#619041), Tumoral calcinosis, familial, normophosphatemic (MIM#610455); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1577 LIPA Lilian Downie Marked gene: LIPA as ready
Prepair 1000+ v1.1577 LIPA Lilian Downie Gene: lipa has been classified as Green List (High Evidence).
Prepair 1000+ v1.1577 LIPA Lilian Downie Phenotypes for gene: LIPA were changed from Cholesteryl ester storage disease, 278000 (3) to Wolman disease, MIM#620151; Cholesteryl ester storage disease, MIM#278000
Prepair 1000+ v1.1576 HADHA Lauren Rogers reviewed gene: HADHA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: LCHAD deficiency MIM#609016, Mitochondrial trifunctional protein deficiency 1 MIM#609015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1576 LIPA Lilian Downie Publications for gene: LIPA were set to
Prepair 1000+ v1.1575 APC2 Lilian Downie Marked gene: APC2 as ready
Prepair 1000+ v1.1575 APC2 Lilian Downie Added comment: Comment when marking as ready: Upgrade to green at review
Prepair 1000+ v1.1575 APC2 Lilian Downie Gene: apc2 has been removed from the panel.
Prepair 1000+ v1.1575 APC2 Lilian Downie Tag for review tag was added to gene: APC2.
Prepair 1000+ v1.1575 OXCT1 Lilian Downie Marked gene: OXCT1 as ready
Prepair 1000+ v1.1575 OXCT1 Lilian Downie Added comment: Comment when marking as ready: Green at review
Prepair 1000+ v1.1575 OXCT1 Lilian Downie Gene: oxct1 has been removed from the panel.
Prepair 1000+ v1.1575 OXCT1 Lilian Downie Phenotypes for gene: OXCT1 were changed from to Succinyl CoA:3-oxoacid CoA transferase deficiency MIM#245050
Prepair 1000+ v1.1574 OXCT1 Lilian Downie Publications for gene: OXCT1 were set to
Prepair 1000+ v1.1573 GNPTG Lauren Rogers reviewed gene: GNPTG: Rating: GREEN; Mode of pathogenicity: None; Publications: 10712439, 19370764:19659762, 33507475, 33023972, 32651481; Phenotypes: Mucolipidosis III gamma, MIM# 252605; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1573 TMEM5 Lilian Downie Marked gene: TMEM5 as ready
Prepair 1000+ v1.1573 TMEM5 Lilian Downie Gene: tmem5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1573 TMEM5 Lilian Downie Publications for gene: TMEM5 were set to
Prepair 1000+ v1.1572 TNNT1 Lilian Downie Marked gene: TNNT1 as ready
Prepair 1000+ v1.1572 TNNT1 Lilian Downie Gene: tnnt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1572 TNNT1 Lilian Downie Phenotypes for gene: TNNT1 were changed from Nemaline myopathy 5, Amish type, 605355 (3) to Nemaline myopathy 5A, autosomal recessive, severe infantile, MIM# 605355; Nemaline myopathy 5B, autosomal recessive, childhood-onset, MIM# 620386
Prepair 1000+ v1.1571 TNNT1 Lilian Downie Publications for gene: TNNT1 were set to
Prepair 1000+ v1.1570 UNC80 Lilian Downie Marked gene: UNC80 as ready
Prepair 1000+ v1.1570 UNC80 Lilian Downie Gene: unc80 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1570 UNC80 Lilian Downie Publications for gene: UNC80 were set to
Prepair 1000+ v1.1569 FLVCR2 Lilian Downie Marked gene: FLVCR2 as ready
Prepair 1000+ v1.1569 FLVCR2 Lilian Downie Gene: flvcr2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1569 FLVCR2 Lilian Downie Publications for gene: FLVCR2 were set to
Prepair 1000+ v1.1568 DLAT Lilian Downie Marked gene: DLAT as ready
Prepair 1000+ v1.1568 DLAT Lilian Downie Added comment: Comment when marking as ready: Upgrade to green
Prepair 1000+ v1.1568 DLAT Lilian Downie Gene: dlat has been removed from the panel.
Prepair 1000+ v1.1568 FLVCR2 Lauren Rogers reviewed gene: FLVCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30712878, 20206334, 20518025, 20690116, 25677735; Phenotypes: Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome, MIM# 225790; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 DLAT Andrew Coventry gene: DLAT was added
gene: DLAT was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: DLAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLAT were set to 34138529; 16049940; 20022530; 29093066
Phenotypes for gene: DLAT were set to Leigh syndrome MONDO:0009723; Pyruvate dehydrogenase E2 deficiency MIM#245348
Review for gene: DLAT was set to GREEN
Added comment: Clinical presentation is in infancy. Pyruvate dehydrogenase E2 deficiency is a mitochondrial disorder, mostly affects the brain and leads to decreased ATP production and energy deficit. Can manifest as a syndrome of neurologic signs (congenital microcephaly, hypotonia, epilepsy, and/or ataxia), brain impacts (dysgenesis of the corpus callosum, Leigh syndrome) and metabolic abnormalities (increased plasma pyruvate, lactic acidemia, and/or metabolic acidosis).
Biochemical function, expression data, and model systems available.

1-4% of total PDE2D cases are due to variants in DLAT - associated with phenotype w/survival into childhood/adulthood, milder than other genes involved with condition.

PMID: 16049940 - 2 unrelated patients with Episodic dystonia. Hypotonia and ataxia, being less prominent. Neuroradiological evidence of discrete lesions restricted to the globus pallidus,
Male patient 1 - dystonic movements of the facial muscles and of his hands and feet.Developmental delay (12 words at age 4). Treatment has improved condition.
Male patient 2 - presented at 11 months of age with episodic dystonia (up to 3hrs duration). 8 years of age, developmental delay, cannot walk.
PMID: 29093066 - 2 siblings (both homozygous for c.470T>G; p.Val157Gly). Male sibling reported with intellectual disability and exercise-induced gait abnormalities. IQ of 44 at 8 years of age. Female sibling noted to have global delays with intellectual disability.
PMID: 20022530 - two sisters with early onset episodic dystonia and pyruvate dehydrogenase deficiency.

At least 6 cases, in 4 unrelated families as described in publications above. While reportedly milder than other presentations, appears severe presentation in absence of treatment. Other genes currently included: PDHA1, PDHB, PDP1.
Sources: Literature
Prepair 1000+ v1.1568 UNC80 Lauren Thomas reviewed gene: UNC80: Rating: GREEN; Mode of pathogenicity: None; Publications: 26708753, 26708751, 30167850, 30771478; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 TNNT1 Lauren Thomas reviewed gene: TNNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26296490, 31604653, 10952871, 24689076; Phenotypes: Nemaline myopathy 5A, autosomal recessive, severe infantile, MIM# 605355, Nemaline myopathy 5B, autosomal recessive, childhood-onset, MIM# 620386; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 TMEM5 Lauren Thomas reviewed gene: TMEM5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23519211, 23217329; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 OXCT1 Andrew Coventry reviewed gene: OXCT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30799594, 20652411, 25778941, 10964512, 8751852, 23420214; Phenotypes: Succinyl CoA:3-oxoacid CoA transferase deficiency MIM#245050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 APC2 Andrew Coventry gene: APC2 was added
gene: APC2 was added to Prepair 1000+. Sources: Literature
Mode of inheritance for gene: APC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APC2 were set to 31585108
Phenotypes for gene: APC2 were set to Cortical dysplasia, complex, with other brain malformations 10 MIM#618677; Intellectual developmental disorder, autosomal recessive 74 MIM#617169; Lissencephaly spectrum disorders MONDO:0018838
Review for gene: APC2 was set to GREEN
Added comment: 12 individuals from 8 unrelated families; intellectual disability, seizures, cortical dysplasia including posterior to anterior predominant pattern of lissencephaly, heterotopias, paucity of white matter, thin corpus callosum.
Definitive classification by ClinGen.
Mouse model present.

Note: Gene has also been implicated in Sotos Syndrome Type 3 which features intellectual disability and characteristic facial features
Sources: Literature
Mendeliome v1.2368 CFAP54 Zornitza Stark Marked gene: CFAP54 as ready
Mendeliome v1.2368 CFAP54 Zornitza Stark Gene: cfap54 has been classified as Red List (Low Evidence).
Mendeliome v1.2368 CFAP54 Zornitza Stark gene: CFAP54 was added
gene: CFAP54 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP54 were set to 26224312; 36593121
Phenotypes for gene: CFAP54 were set to Spermatogenic failure 98, MIM# 621124; Hydrocephalus, male infertility, mucus accumulation
Review for gene: CFAP54 was set to RED
Added comment: PMID 36593121: Three men identified with bi-allelic variants and multiple morphologic abnormalities of the flagella or non-obstructive azoospermia.

PMID: 26224312: Homozygous mice have PCD characterized by hydrocephalus, male infertility (spermatogenesis defects in flagella maturation), and mucus accumulation. Brain analysis showed mild dilatation of the lateral ventricles. Tracheal cilia beat frequency was significantly reduced. The gene was highest expressed in the testis and lungs
Sources: Literature
Ciliary Dyskinesia v1.44 CFAP54 Zornitza Stark Publications for gene: CFAP54 were set to PMID: 26224312
Ciliary Dyskinesia v1.43 CFAP54 Zornitza Stark edited their review of gene: CFAP54: Changed publications: 36593121
Ciliary Dyskinesia v1.43 CFAP54 Zornitza Stark Phenotypes for gene: CFAP54 were changed from Hydrocephalus, male infertility, mucus accumulation to Spermatogenic failure 98, MIM# 621124; Hydrocephalus, male infertility, mucus accumulation
Ciliary Dyskinesia v1.42 CFAP54 Zornitza Stark reviewed gene: CFAP54: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 98, MIM# 621124; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2367 BUD13 Zornitza Stark Phenotypes for gene: BUD13 were changed from Lipodystrophy, MONDO:0006573 to Achalasia-progeroid syndrome, MIM# 621123
Mendeliome v1.2366 BUD13 Zornitza Stark reviewed gene: BUD13: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Achalasia-progeroid syndrome, MIM# 621123; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lipodystrophy_Lipoatrophy v1.18 BUD13 Zornitza Stark Phenotypes for gene: BUD13 were changed from Lipodystrophy, MONDO:0006573 to Achalasia-progeroid syndrome, MIM# 621123
Lipodystrophy_Lipoatrophy v1.17 BUD13 Zornitza Stark reviewed gene: BUD13: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Achalasia-progeroid syndrome, MIM# 621123; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 LIPA Karina Sandoval reviewed gene: LIPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 28374935, 11487567, 8617513, 21963785; Phenotypes: Wolman disease, MIM#620151, Cholesteryl ester storage disease, MIM#278000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 LIFR Karina Sandoval reviewed gene: LIFR: Rating: GREEN; Mode of pathogenicity: None; Publications: 9674905, 9674906, 14740318, 24988918, 35663789, 20447141, 29620724, 28334964; Phenotypes: Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome, MIM#601559; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 L1CAM Karina Sandoval reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 11438988, 7920660, 8401593, 19565280, 9279760, 11857550, 15148591, 15368500, 22354677; Phenotypes: MASA syndrome, MIM#303350, Hydrocephalus, congenital, X-linked, MIM#307000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.1568 KDM5C Karina Sandoval reviewed gene: KDM5C: Rating: GREEN; Mode of pathogenicity: None; Publications: 15586325, 32279304; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type, MIM#300534; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.1568 IQSEC2 Karina Sandoval changed review comment from: De novo variants and PTCs in females are severe, while inherited missense are milder. Females with these missense may be asymptomatic or show mild intellectual disability (PMID: 31415821). Autistic features are common.

Missense can be both GOF or LOF.

More than 20 unrelated families reported.; to: De novo variants and PTCs in females are severe, while inherited missense are milder. Females with these missense may be asymptomatic or show mild intellectual disability (PMID: 31415821). Autistic features are common.

Missense can be both GOF or LOF.

More than 20 unrelated families reported.

ClinGen: Definitive gene-disease association - The affected individuals, including both males and females, typically have intellectual disability with variable seizures, autistic traits, and psychiatric problems. Males are generally more severely affected compared with females.
Prepair 1000+ v1.1568 IQSEC2 Karina Sandoval reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33368194, 20473311, 23674175, 31415821, 30842726; Phenotypes: Intellectual developmental disorder, X-linked 1, MIM#309530; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.1568 IGF1R Karina Sandoval reviewed gene: IGF1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 31586944, 14657428, 25040157, 23045302, 26252249, 15928254, 22130793, 17264177; Phenotypes: Insulin-like growth factor I, resistance to, MIM#270450; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 HOGA1 Karina Sandoval reviewed gene: HOGA1: Rating: RED; Mode of pathogenicity: None; Publications: 20797690, 21896830, 22391140, 36688940; Phenotypes: Hyperoxaluria, primary, type III, MIM#613616; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 HMGCS2 Karina Sandoval reviewed gene: HMGCS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25778941, 9337379, 23751782, 33045405, 32470406, 32259399, 16601895; Phenotypes: HMG-CoA synthase-2 deficiency, MIM#605911; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 HEXA Karina Sandoval reviewed gene: HEXA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31388111, 20301397; Phenotypes: Tay-Sachs disease, GM2-gangliosidosis, several forms, [Hex A pseudodeficiency], MIM#272800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 GUCY2C Karina Sandoval reviewed gene: GUCY2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 22521417, 22436048, 25994218, 30353760, 28957388, 22521417, 33883099, 31079856; Phenotypes: Meconium ileus, MIM#614665; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 GPR179 Karina Sandoval reviewed gene: GPR179: Rating: GREEN; Mode of pathogenicity: None; Publications: 22325361; Phenotypes: Night blindness, congenital stationary (complete), 1E, autosomal recessive, MIM#614565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 GJC2 Karina Sandoval reviewed gene: GJC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19056803, 31431325, 25059390, 20537300, 21266381, 15192806, 18094336, 22669416, 24374284, 15192806; Phenotypes: Leukodystrophy, hypomyelinating, 2, MIM#608804; Mode of inheritance: None
Epidermolysis bullosa v1.22 CSTB Dmitrijs Rots reviewed gene: CSTB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v1.1568 GAA Karina Sandoval reviewed gene: GAA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25103075, 27365701, 29880332; Phenotypes: Glycogen storage disease II, MIM#232300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2366 KCNQ1OT1 Zornitza Stark Classified gene: KCNQ1OT1 as Amber List (moderate evidence)
Mendeliome v1.2366 KCNQ1OT1 Zornitza Stark Gene: kcnq1ot1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.1568 EIF2AK4 Karina Sandoval changed review comment from: Slowly progressive and ultimately fatal without a lung transplant. Age of onset in 3rd decade.

Pulmonary hypertension is a feature of the condition
Severe; yes. Early onset; ?

PMID:24135949 - 2 affected sibs, aged 19y & 33y at diagnosis. And 2x sporadic cases at 22y & 15y

PMID: 24292273 - 13 families with 19 affected individuals. Age of PVOD diagnosis 3x 2nd decade (aged 11, 15 & 19), 9x 3rd decade, 4x 4th decade, 2x 5th decade, 1x 6th decade; to: Slowly progressive and ultimately fatal without a lung transplant. Age of onset in 3rd decade.

Pulmonary hypertension is a feature of the condition

Well established gene-disease assoc. Severe; yes. Early onset; varies

PMID:24135949 - 2 affected sibs, aged 19y & 33y at diagnosis. And 2x sporadic cases at 22y & 15y

PMID: 24292273 - 13 families with 19 affected individuals. Age of PVOD diagnosis 3x 2nd decade (aged 11, 15 & 19), 9x 3rd decade, 4x 4th decade, 2x 5th decade, 1x 6th decade
Prepair 1000+ v1.1568 EIF2AK4 Karina Sandoval reviewed gene: EIF2AK4: Rating: AMBER; Mode of pathogenicity: None; Publications: 24135949, 24292273; Phenotypes: Pulmonary venoocclusive disease 2, MIM#234810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 DYNC2H1 Karina Sandoval reviewed gene: DYNC2H1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19442771, 19361615, 22499340, 23456818, 27925158, 32753734, 31730820, 32753734; Phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM#613091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 DNAJC6 Karina Sandoval reviewed gene: DNAJC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 33983693, 22563501, 23211418, 26528954; Phenotypes: Parkinson disease 19a, juvenile-onset, MIM#615528; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.80 PIGW Zornitza Stark Classified gene: PIGW as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.80 PIGW Zornitza Stark Gene: pigw has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.79 PIGW Zornitza Stark edited their review of gene: PIGW: Added comment: Downgraded to AMBER, assessed as LIMITED by ClinGen.; Changed rating: AMBER
Genetic Epilepsy v1.118 PIGW Zornitza Stark Classified gene: PIGW as Amber List (moderate evidence)
Genetic Epilepsy v1.118 PIGW Zornitza Stark Gene: pigw has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v1.117 PIGW Zornitza Stark edited their review of gene: PIGW: Added comment: Downgraded to AMBER, assessed as LIMITED by ClinGen.; Changed rating: AMBER
Congenital Disorders of Glycosylation v1.60 PIGW Zornitza Stark Phenotypes for gene: PIGW were changed from Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025; intractable seizures; West syndrome; severe developmental delay; dysmorphic facial features; hyperphosphatasia; epilepsy; recurrent respiratory infections; hypotonia; stereotypies to Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025
Prepair 1000+ v1.1568 DNAJC21 Karina Sandoval reviewed gene: DNAJC21: Rating: GREEN; Mode of pathogenicity: None; Publications: 29700810, 28062395, 27346687; Phenotypes: Bone marrow failure syndrome 3, MIM#617052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.59 PIGW Zornitza Stark Classified gene: PIGW as Amber List (moderate evidence)
Congenital Disorders of Glycosylation v1.59 PIGW Zornitza Stark Gene: pigw has been classified as Amber List (Moderate Evidence).
Congenital Disorders of Glycosylation v1.58 PIGW Zornitza Stark reviewed gene: PIGW: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 11, MIM# 616025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2365 PIGW Zornitza Stark Classified gene: PIGW as Amber List (moderate evidence)
Mendeliome v1.2365 PIGW Zornitza Stark Gene: pigw has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2364 PIGW Zornitza Stark edited their review of gene: PIGW: Added comment: Downgraded to AMBER in light of ClinGen's assessment as LIMITED.; Changed rating: AMBER
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.156 KIAA1549 Zornitza Stark Marked gene: KIAA1549 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.156 KIAA1549 Zornitza Stark Gene: kiaa1549 has been classified as Green List (High Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.156 KIAA1549 Zornitza Stark edited their review of gene: KIAA1549: Changed phenotypes: retinitis pigmentosa 86 MONDO:0032834
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.156 KIAA1549 Zornitza Stark reviewed gene: KIAA1549: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.156 KIAA1549 Zornitza Stark Phenotypes for gene: KIAA1549 were changed from Retinitis pigmentosa 86 to retinitis pigmentosa 86 MONDO:0032834
Mendeliome v1.2364 KIAA1549 Zornitza Stark Marked gene: KIAA1549 as ready
Mendeliome v1.2364 KIAA1549 Zornitza Stark Gene: kiaa1549 has been classified as Green List (High Evidence).
Mendeliome v1.2364 KIAA1549 Zornitza Stark Classified gene: KIAA1549 as Green List (high evidence)
Mendeliome v1.2364 KIAA1549 Zornitza Stark Gene: kiaa1549 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1568 DNAAF4 Karina Sandoval reviewed gene: DNAAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23872636; Phenotypes: Ciliary dyskinesia, primary, 25, MIM#615482; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 DHCR24 Karina Sandoval reviewed gene: DHCR24: Rating: GREEN; Mode of pathogenicity: None; Publications: 33524375, 21671375, 12457401, 29175559, 21559050, 29175559, 11519011, 24961299; Phenotypes: Desmosterolosis, MIM#602398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2363 KIAA1549 Sangavi Sivagnanasundram gene: KIAA1549 was added
gene: KIAA1549 was added to Mendeliome. Sources: ClinGen
Mode of inheritance for gene: KIAA1549 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1549 were set to 30120214; 34027671
Phenotypes for gene: KIAA1549 were set to retinitis pigmentosa 86 MONDO:0032834
Review for gene: KIAA1549 was set to GREEN
Added comment: Classified as STRONG by ClinGen Retina GCEP on 18/02/2025 - https://search.clinicalgenome.org/CCID:008708

Reported in 5 probands with RP - Green according to PanelApp
Sources: ClinGen
Mendeliome v1.2363 IFT74 Sangavi Sivagnanasundram reviewed gene: IFT74: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: primary ciliary dyskinesia, MONDO:0016575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2363 PIGW Sangavi Sivagnanasundram reviewed gene: PIGW: Rating: GREEN; Mode of pathogenicity: None; Publications: 34618440; Phenotypes: hyperphosphatasia with intellectual disability syndrome 5 MONDO:0014457; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2363 MYL1 Sangavi Sivagnanasundram reviewed gene: MYL1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: congenital myopathy MONDO:0019952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2363 DEF6 Sangavi Sivagnanasundram reviewed gene: DEF6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: immunodeficiency 87 and autoimmunity MONDO:0030457; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 ZNF469 Cassandra Muller reviewed gene: ZNF469: Rating: GREEN; Mode of pathogenicity: None; Publications: 33739556, 37098112, 31496642, 18452888; Phenotypes: Brittle cornea syndrome 1, 229200, (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 XPC Cassandra Muller changed review comment from: Strong gene disease association.; to: Strong gene disease association. Severe DNA repair disorder, early childhood onset. Characterized by increased sensitivity to ultraviolet (UV) irradiation and increased risk of skin cancer. Can cause premature death.
Prepair 1000+ v1.1568 XPC Cassandra Muller reviewed gene: XPC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26255934, 8298653; Phenotypes: Xeroderma pigmentosum, group C, 278720 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 WRAP53 Cassandra Muller reviewed gene: WRAP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 21205863, 29514627, 32303682; Phenotypes: Dyskeratosis congenita, autosomal recessive 3, 613988 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.124 ELF4 Zornitza Stark Phenotypes for gene: ELF4 were changed from Inflammatory bowel disease to Autoinflammatory syndrome, familial, X-linked, Behcet-like 2 (MIM#301074)
Inflammatory bowel disease v0.123 ELF4 Zornitza Stark reviewed gene: ELF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory syndrome, familial, X-linked, Behcet-like 2 (MIM#301074); Mode of inheritance: None
Mendeliome v1.2363 ELF4 Zornitza Stark Marked gene: ELF4 as ready
Mendeliome v1.2363 ELF4 Zornitza Stark Gene: elf4 has been classified as Green List (High Evidence).
Mendeliome v1.2363 SLC25A25 Zornitza Stark Marked gene: SLC25A25 as ready
Mendeliome v1.2363 SLC25A25 Zornitza Stark Gene: slc25a25 has been classified as Red List (Low Evidence).
Mendeliome v1.2363 SLC25A25 Zornitza Stark gene: SLC25A25 was added
gene: SLC25A25 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC25A25 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC25A25 were set to 34346195
Phenotypes for gene: SLC25A25 were set to Nephrolithiasis MONDO:0008171,SLC25A25 related
Penetrance for gene: SLC25A25 were set to Incomplete
Review for gene: SLC25A25 was set to RED
Added comment: SLC25A25 encodes mitochondrial ATP-Mg/Pi carrier 3

A single missense variant was reported in 2 families with renal stones in 2021 by Jabalameli et al (PMID: 3436195).
In family 1 there was 4 affected individuals who shared the same heterozygous variant NM_001330988.2 c.1083G>C|p.Gln361His, however this variant was also seen in 7 individuals in the family without stones
In family 2 there were 7 affected individuals who also had p.Gln361His however this variant was also seen in 3 family members without stones.

This variant is located within the mitochondrial carrier domain and functional studies were performed looking at uptake of radioactive ATP compared to wild type. These studies demonstrated the variant protein had approximately 21% activity compared to wild type.

The variant was proposed to have incomplete penetrance and it should be noted there is 4352 heterozygotes in gnomad 4.

At this time there is insufficient evidence for a gene disease association between SLC25A25 and nephrolithiasis.
Sources: Literature
Mendeliome v1.2362 ELF4 Bryony Thompson Classified gene: ELF4 as Green List (high evidence)
Mendeliome v1.2362 ELF4 Bryony Thompson Gene: elf4 has been classified as Green List (High Evidence).
Mendeliome v1.2360 ELF4 Bryony Thompson gene: ELF4 was added
gene: ELF4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ELF4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ELF4 were set to 38231408
Phenotypes for gene: ELF4 were set to autoinflammatory syndrome, familial, X-linked, Behcet-like 2 MONDO:0024770
Inflammatory bowel disease v0.123 ELF4 Bryony Thompson Marked gene: ELF4 as ready
Inflammatory bowel disease v0.123 ELF4 Bryony Thompson Gene: elf4 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.123 ELF4 Bryony Thompson Classified gene: ELF4 as Green List (high evidence)
Inflammatory bowel disease v0.123 ELF4 Bryony Thompson Gene: elf4 has been classified as Green List (High Evidence).
Renal Tubulopathies and related disorders v1.18 SLC25A25 Zornitza Stark Marked gene: SLC25A25 as ready
Renal Tubulopathies and related disorders v1.18 SLC25A25 Zornitza Stark Gene: slc25a25 has been classified as Red List (Low Evidence).
Renal Tubulopathies and related disorders v1.18 SLC25A25 Zornitza Stark Classified gene: SLC25A25 as Red List (low evidence)
Renal Tubulopathies and related disorders v1.18 SLC25A25 Zornitza Stark Gene: slc25a25 has been classified as Red List (Low Evidence).
Renal Tubulopathies and related disorders v1.17 SLC25A25 Sarah Milton gene: SLC25A25 was added
gene: SLC25A25 was added to Renal Tubulopathies and related disorders. Sources: Literature
Mode of inheritance for gene: SLC25A25 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC25A25 were set to 34346195
Phenotypes for gene: SLC25A25 were set to Nephrolithiasis MONDO:0008171,SLC25A25 related
Penetrance for gene: SLC25A25 were set to Incomplete
Review for gene: SLC25A25 was set to RED
Added comment: SLC25A25 encodes mitochondrial ATP-Mg/Pi carrier 3

A single missense variant was reported in 2 families with renal stones in 2021 by Jabalameli et al (PMID: 3436195).
In family 1 there was 4 affected individuals who shared the same heterozygous variant NM_001330988.2 c.1083G>C|p.Gln361His, however this variant was also seen in 7 individuals in the family without stones
In family 2 there were 7 affected individuals who also had p.Gln361His however this variant was also seen in 3 family members without stones.

This variant is located within the mitochondrial carrier domain and functional studies were performed looking at uptake of radioactive ATP compared to wild type. These studies demonstrated the variant protein had approximately 21% activity compared to wild type.

The variant was proposed to have incomplete penetrance and it should be noted there is 4352 heterozygotes in gnomad 4.

At this time there is insufficient evidence for a gene disease association between SLC25A25 and nephrolithiasis.
Sources: Literature
Prepair 1000+ v1.1568 FERMT3 Melanie Marty reviewed gene: FERMT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234460, 19064721; Phenotypes: Leukocyte adhesion deficiency, type III, MIM# 612840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 FBP1 Melanie Marty reviewed gene: FBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fructose-1,6-bisphosphatase deficiency, MIM# 229700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 FANCA Melanie Marty reviewed gene: FANCA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group A, MIM# 227650, MONDO:0009215; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 FAM126A Melanie Marty reviewed gene: FAM126A: Rating: GREEN; Mode of pathogenicity: None; Publications: 16951682, 21911699, 23998934, 22749724; Phenotypes: Leukodystrophy, hypomyelinating, 5 MIM#610532; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 FAH Melanie Marty reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: None; Publications: 8253378, 1401056, 8364576, 8318997, 25681080; Phenotypes: Tyrosinaemia, type I, MIM# 276700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 ERCC5 Melanie Marty reviewed gene: ERCC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 7951246, 9096355, 9096355, 24700531, 33766032, 33219753; Phenotypes: Cerebrooculofacioskeletal syndrome 3, MIM# 616570, MONDO:0014696, Xeroderma pigmentosum, group G, MIM# 278780, MONDO:0010216; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia - paediatric v1.87 AFG3L2 Chirag Patel Publications for gene: AFG3L2 were set to 22022284; 25401298; 20208537; 20725928; 33075064; 32248051; 30910913
Aortopathy_Connective Tissue Disorders v1.87 ATP6V1A Chirag Patel Classified gene: ATP6V1A as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v1.87 ATP6V1A Chirag Patel Gene: atp6v1a has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.87 ATP6V1A Chirag Patel Classified gene: ATP6V1A as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v1.87 ATP6V1A Chirag Patel Gene: atp6v1a has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.87 ATP6V1A Chirag Patel Classified gene: ATP6V1A as Green List (high evidence)
Aortopathy_Connective Tissue Disorders v1.87 ATP6V1A Chirag Patel Gene: atp6v1a has been classified as Green List (High Evidence).
Mendeliome v1.2359 ATP5A1 Chirag Patel Publications for gene: ATP5A1 were set to 23599390
Prepair 1000+ v1.1568 TTN Andrew Coventry reviewed gene: TTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 12145747, 17444505, 3975875, 24105469, 24395473, 25772186, 26392295, 26581302, 27796757, 28040389, 29575618, 29691892, 31660661; Phenotypes: TTN-related myopathy MONDO:0100175; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dyslipidaemia v0.45 APOA1 Chirag Patel Mode of inheritance for gene: APOA1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dyslipidaemia v0.44 APOA1 Chirag Patel Mode of inheritance for gene: APOA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v1.2358 APOA1 Chirag Patel Mode of inheritance for gene: APOA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2357 APOA1 Chirag Patel Mode of inheritance for gene: APOA1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dyslipidaemia v0.43 APOA1 Chirag Patel Mode of inheritance for gene: APOA1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.1568 AMN Andrew Coventry reviewed gene: AMN: Rating: AMBER; Mode of pathogenicity: None; Publications: 12590260, 15024727, 17285242, 24156255, 26040326, 27604308; Phenotypes: Imerslund-Grasbeck syndrome 2 MIM#618882; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 DBR1 Andrew Coventry reviewed gene: DBR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37656279, 29474921, 38325642; Phenotypes: Xerosis and growth failure with immune and pulmonary dysfunction syndrome MIM#620510, Viral infections of the brainstem, Ichthyosis (MONDO#0019269); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 HPDL Andrew Coventry reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: 32707086, 33188300, 33634263, 33970200, 18853439; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities MIM#619026, Spastic paraplegia 83, autosomal recessive MIM#619027, Leigh syndrome MONDO:0009723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 SCN1B Andrew Coventry reviewed gene: SCN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 36291443, 31709768, 19710327, 23148524, 28218389, 33901312; Phenotypes: Developmental and epileptic encephalopathy 52 MIM#617350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2356 SLC9A6 Zornitza Stark Phenotypes for gene: SLC9A6 were changed from Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; MONDO:0010278 to Intellectual developmental disorder, X-linked syndromic, Christianson type MIM#300243; Neurodegenerative disorder, X-linked, female-restricted, with parkinsonism and cognitive impairement, MIM# 301142
Mendeliome v1.2355 SLC9A6 Zornitza Stark Publications for gene: SLC9A6 were set to 18342287; 19377476; 25044251; 33278113; 32569089; 31879735
Mendeliome v1.2354 SLC9A6 Zornitza Stark edited their review of gene: SLC9A6: Added comment: Multiple female carriers reported with adult-onset neurological phenotypes including neurodegerative disease and Parkinsonism. Some had affected sons with ID. Uncertain whether this is a separate entity or manifestation in female carriers of a XL condition.; Changed publications: 18342287, 19377476, 25044251, 33278113, 32569089, 31879735, 35198730, 39810750, 35198730, 31192222; Changed phenotypes: Intellectual developmental disorder, X-linked syndromic, Christianson type MIM#300243, Neurodegenerative disorder, X-linked, female-restricted, with parkinsonism and cognitive impairement, MIM# 301142
Early-onset Parkinson disease v2.12 SLC9A6 Zornitza Stark Marked gene: SLC9A6 as ready
Early-onset Parkinson disease v2.12 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.12 SLC9A6 Zornitza Stark Classified gene: SLC9A6 as Green List (high evidence)
Early-onset Parkinson disease v2.12 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v2.11 SLC9A6 Zornitza Stark gene: SLC9A6 was added
gene: SLC9A6 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SLC9A6 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SLC9A6 were set to 35198730; 39810750; 35198730; 31192222
Phenotypes for gene: SLC9A6 were set to Neurodegenerative disorder, X-linked, female-restricted, with parkinsonism and cognitive impairement, MIM# 301142
Review for gene: SLC9A6 was set to GREEN
Added comment: Multiple female carriers reported with adult-onset neurological phenotypes including neurodegerative disease and Parkinsonism. Some had affected sons with ID. Uncertain whether this is a separate entity or manifestation in female carriers of a XL condition.
Sources: Literature
Early-onset Dementia v1.32 SLC9A6 Zornitza Stark Mode of inheritance for gene: SLC9A6 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Dementia v1.31 SLC9A6 Zornitza Stark edited their review of gene: SLC9A6: Changed phenotypes: Neurodegenerative disorder, X-linked, female-restricted, with parkinsonism and cognitive impairement, MIM# 301142; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early-onset Dementia v1.31 SLC9A6 Zornitza Stark Marked gene: SLC9A6 as ready
Early-onset Dementia v1.31 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Early-onset Dementia v1.31 SLC9A6 Zornitza Stark Classified gene: SLC9A6 as Green List (high evidence)
Early-onset Dementia v1.31 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Early-onset Dementia v1.30 SLC9A6 Zornitza Stark gene: SLC9A6 was added
gene: SLC9A6 was added to Early-onset Dementia. Sources: Literature
Mode of inheritance for gene: SLC9A6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC9A6 were set to 35198730; 39810750; 35198730; 31192222
Phenotypes for gene: SLC9A6 were set to Neurodegenerative disorder, X-linked, female-restricted, with parkinsonism and cognitive impairement, MIM# 301142
Review for gene: SLC9A6 was set to GREEN
Added comment: Multiple female carriers reported with adult-onset neurological phenotypes including neurodegerative disease and Parkinsonism. Some had affected sons with ID. Uncertain whether this is a separate entity or manifestation in female carriers of a XL condition.
Sources: Literature
Mendeliome v1.2354 CFAP47 Zornitza Stark Phenotypes for gene: CFAP47 were changed from Spermatogenic failure, X-linked, 3, MIM# 301059; asthenoteratozoospermia; morphological abnormalities of the flagella (MMAF) to Spermatogenic failure, X-linked, 3, MIM# 301059; Cystic kidney disease MONDO:0002473
Mendeliome v1.2353 CFAP47 Zornitza Stark Publications for gene: CFAP47 were set to PMID: 33472045
Prepair 1000+ v1.1568 USH2A Cassandra Muller reviewed gene: USH2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20507924, 9624053, 15015129, 20301515, 36041150, 34331125; Phenotypes: Usher syndrome, type 2A, 276901 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 UFM1 Cassandra Muller reviewed gene: UFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28931644, 29868776; Phenotypes: Leukodystrophy, hypomyelinating, 14, 617899 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1568 SMPD1 Lilian Downie Marked gene: SMPD1 as ready
Prepair 1000+ v1.1568 SMPD1 Lilian Downie Gene: smpd1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.1568 SMPD1 Lilian Downie Phenotypes for gene: SMPD1 were changed from Niemann-Pick disease, type A, 257200 (3) to Niemann-Pick disease, type A, 257200; Niemann-Pick disease, type B, 607616
Prepair 1000+ v1.1567 SMPD1 Lilian Downie Publications for gene: SMPD1 were set to
Prepair 1000+ v1.1566 PTPN23 Lilian Downie Marked gene: PTPN23 as ready
Prepair 1000+ v1.1566 PTPN23 Lilian Downie Added comment: Comment when marking as ready: UPGRADE TO GREEN
Prepair 1000+ v1.1566 PTPN23 Lilian Downie Gene: ptpn23 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.1566 TYMP Cassandra Muller reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 9924029; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type), 603041 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v1.19 BAG3 Chirag Patel edited their review of gene: BAG3: Added comment: PMID: 37907725
7 individuals from the one family with distal motor neuronopathy (mean age of onset ~46 years). They presented with slowly progressive and symmetric distal weakness and atrophy of lower limb muscles, absent Achilles reflexes, and neurogenic changes on muscle biopsies. There were no sensory abnormalities or signs of myofibrillar myopathy. WES with segregation analysis identified a novel heterozygous truncating variant in the gene BAG3 in all affected family members [c.1513_1514insGGAC (p.Val505GlyfsTer6)]. There was autosomal dominant inheritance with incomplete penetrance in women. Western blot analysis of muscle tissue from 2 individuals showed presence of a truncated BAG3 protein. Functional studies of the variant were not performed.

PMID: 31853710
2 individuals from a Chinese family with adult-onset and moderate CMT. Nerve conduction velocity studies and sural nerve biopsy revealed an axonal sensorimotor neuropathy. MRI showed fatty infiltration more severe in the soleus and deep posterior compartment muscles. WES identified a missense variant (p.Pro209Ser) in BAG3 gene, which co-segregated with the CMT disease in the family. Functional studies of the variant were not performed.

PMID: 30145633
1 individual with axonal sensory-motor polyneuropathy, myopathy (and raised CK levels), rigid spine syndrome, and respiratory dysfunction (but no cardiomyopathy). MRI showed bilateral symmetric fatty atrophy of muscles at the lower limb and paraspinal muscles. WES identified the same missense variant (p.Pro209Ser) in BAG3 gene, and it was de novo in the individual. Functional studies of the variant were not performed.

PMID: 28754666
9 affected individuals from 2 large multigenerational families with CMT phenotype, but no evidence of a myopathy. WES identified the same missense variant (p.Pro209Ser) in BAG3 gene, which co-segregated with the CMT disease in the family. Functional studies of the variant were not performed.; Changed publications: PMID: 37907725, 31853710, 30145633, 28754666
Mendeliome v1.2352 BAG3 Chirag Patel reviewed gene: BAG3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37907725, 31853710, 30145633, 28754666; Phenotypes: Neuronopathy, distal hereditary motor, autosomal dominant MONDO:0015362, Charcot-Marie-Tooth disease type 2 MONDO: 0018993; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy - complex v1.19 BAG3 Chirag Patel Deleted their comment
Hereditary Neuropathy - complex v1.19 BAG3 Chirag Patel changed review comment from: PMID: 37907725
7 individuals from the one family with distal motor neuronopathy (mean age of onset ~46 years). They presented with slowly progressive and symmetric distal weakness and atrophy of lower limb muscles, absent Achilles reflexes, and neurogenic changes on muscle biopsies. There were no sensory abnormalities or signs of myofibrillar myopathy. WES with segregation analysis identified a novel heterozygous truncating variant in the gene BAG3 in all affected family members [c.1513_1514insGGAC (p.Val505GlyfsTer6)]. There was autosomal dominant inheritance with incomplete penetrance in women. Western blot analysis of muscle tissue from 2 individuals showed presence of a truncated BAG3 protein. Functional studies of the variant were not performed.

PMID: 31853710
2 individuals from a Chinese family with adult-onset and moderate CMT. Nerve conduction velocity studies and sural nerve biopsy revealed an axonal sensorimotor neuropathy. MRI showed fatty infiltration more severe in the soleus and deep posterior compartment muscles. WES identified a missense variant (p.Pro209Ser) in BAG3 gene, which co-segregated with the CMT disease in the family. Functional studies of the variant were not performed.

PMID: 30145633
1 individual with axonal sensory-motor polyneuropathy, myopathy (and raised CK levels), rigid spine syndrome, and respiratory dysfunction (but no cardiomyopathy). MRI showed bilateral symmetric fatty atrophy of muscles at the lower limb and paraspinal muscles. WES identified the same missense variant (p.Pro209Ser) in BAG3 gene, and it was de novo in the individual. Functional studies of the variant were not performed.

PMID: 28754666
9 affected individuals from 2 large multigenerational families with CMT phenotype, but no evidence of a myopathy. WES identified the same missense variant (p.Pro209Ser) in BAG3 gene, which co-segregated with the CMT disease in the family. Functional studies of the variant were not performed.; to: PMID: 37907725
7 individuals from the one family with distal motor neuronopathy (mean age of onset ~46 years). They presented with slowly progressive and symmetric distal weakness and atrophy of lower limb muscles, absent Achilles reflexes, and neurogenic changes on muscle biopsies. There were no sensory abnormalities or signs of myofibrillar myopathy. WES with segregation analysis identified a novel heterozygous truncating variant in the gene BAG3 in all affected family members [c.1513_1514insGGAC (p.Val505GlyfsTer6)]. There was autosomal dominant inheritance with incomplete penetrance in women. Western blot analysis of muscle tissue from 2 individuals showed presence of a truncated BAG3 protein. Functional studies of the variant were not performed.

PMID: 31853710
2 individuals from a Chinese family with adult-onset and moderate CMT. Nerve conduction velocity studies and sural nerve biopsy revealed an axonal sensorimotor neuropathy. MRI showed fatty infiltration more severe in the soleus and deep posterior compartment muscles. WES identified a missense variant (p.Pro209Ser) in BAG3 gene, which co-segregated with the CMT disease in the family. Functional studies of the variant were not performed.

PMID: 30145633
1 individual with axonal sensory-motor polyneuropathy, myopathy (and raised CK levels), rigid spine syndrome, and respiratory dysfunction (but no cardiomyopathy). MRI showed bilateral symmetric fatty atrophy of muscles at the lower limb and paraspinal muscles. WES identified the same missense variant (p.Pro209Ser) in BAG3 gene, and it was de novo in the individual. Functional studies of the variant were not performed.

PMID: 28754666
9 affected individuals from 2 large multigenerational families with CMT phenotype, but no evidence of a myopathy. WES identified the same missense variant (p.Pro209Ser) in BAG3 gene, which co-segregated with the CMT disease in the family. Functional studies of the variant were not performed.
Hereditary Neuropathy - complex v1.19 BAG3 Chirag Patel reviewed gene: BAG3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37907725, PMID: 31853710; Phenotypes: Neuronopathy, distal hereditary motor, autosomal dominant MONDO:0015362, Charcot-Marie-Tooth disease type 2 MONDO: 0018993; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.79 PPP2R5E Chirag Patel gene: PPP2R5E was added
gene: PPP2R5E was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPP2R5E was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R5E were set to PMID: 39284558
Phenotypes for gene: PPP2R5E were set to Mendelian neurodevelopmental disorder MONDO:0100500
Review for gene: PPP2R5E was set to RED
Added comment: One 20yrs old individual with learning issues, motor coordination disorders, hypotonia (myopathy on EMG), and behavioural issues (mood and emotional dysregulation). WES testing identified a de novo heterozygous missense variant (Glu191Lys) in PPP2R5E gene. The variant was not found in the 4 healthy brothers of the individual. The variant is located within a conserved LFDSEDPRER motif common to all PPP2R5 B-subunits. Biochemical assays demonstrated a decreased interaction with the PP2A A and C subunits, leading to disturbances in holoenzyme formation.

Protein phosphatase 2A (PP2A) is a family of multifunctional enzymatic complexes crucial for cellular signalling, playing a pivotal role in brain function and development. Mutations in specific genes encoding PP2A complexes have been associated with neurodevelopmental disorders with hypotonia and high risk of seizures (e.g. PP2AR-1A, 2B, 3C, 5C, 5D).
Sources: Literature
Mendeliome v1.2352 PPP2R5E Chirag Patel gene: PPP2R5E was added
gene: PPP2R5E was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP2R5E was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R5E were set to PMID: 39284558
Phenotypes for gene: PPP2R5E were set to Mendelian neurodevelopmental disorder MONDO:0100500
Review for gene: PPP2R5E was set to RED
Added comment: One 20yrs old individual with learning issues, motor coordination disorders, hypotonia (myopathy on EMG), and behavioural issues (mood and emotional dysregulation). WES testing identified a de novo heterozygous missense variant (Glu191Lys) in PPP2R5E gene. The variant was not found in the 4 healthy brothers of the individual. The variant is located within a conserved LFDSEDPRER motif common to all PPP2R5 B-subunits. Biochemical assays demonstrated a decreased interaction with the PP2A A and C subunits, leading to disturbances in holoenzyme formation.

Protein phosphatase 2A (PP2A) is a family of multifunctional enzymatic complexes crucial for cellular signalling, playing a pivotal role in brain function and development. Mutations in specific genes encoding PP2A complexes have been associated with neurodevelopmental disorders with hypotonia and high risk of seizures (e.g. PP2AR-1A, 2B, 3C, 5C, 5D).
Sources: Literature
Renal Macrocystic Disease v0.79 CFAP47 Chirag Patel changed review comment from: 3 individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts or any family history of cystic kidney disease.

WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased.

CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.
Sources: Literature; to: 3 Japanese individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts, infertility, or any family history of cystic kidney disease.

WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased.

CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.
Sources: Literature
Mendeliome v1.2351 CFAP47 Chirag Patel changed review comment from: 3 individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts or any family history of cystic kidney disease. WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased. CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.; to: 3 Japanese individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts, infertility, or any family history of cystic kidney disease. WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased. CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.
Mendeliome v1.2351 CFAP47 Chirag Patel reviewed gene: CFAP47: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 39698362; Phenotypes: Cystic kidney disease MONDO:0002473; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Renal Macrocystic Disease v0.79 CFAP47 Chirag Patel Classified gene: CFAP47 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.79 CFAP47 Chirag Patel Gene: cfap47 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.78 CFAP47 Chirag Patel gene: CFAP47 was added
gene: CFAP47 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: CFAP47 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CFAP47 were set to PMID: 39698362
Phenotypes for gene: CFAP47 were set to Cystic kidney disease MONDO:0002473
Review for gene: CFAP47 was set to AMBER
Added comment: 3 individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts or any family history of cystic kidney disease.

WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased.

CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.
Sources: Literature
Prepair 1000+ v1.1566 TMEM237 Cassandra Muller reviewed gene: TMEM237: Rating: GREEN; Mode of pathogenicity: None; Publications: 22152675, 22152675; Phenotypes: Joubert syndrome 14, 614424 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1566 TMEM231 Cassandra Muller reviewed gene: TMEM231: Rating: GREEN; Mode of pathogenicity: None; Publications: 23012439, 23349226, 22179047, 30617574, 27449316, 31663672, 25869670; Phenotypes: Joubert syndrome 20, 614970, (3), Meckel syndrome 11, 615397 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1566 TMEM165 Cassandra Muller reviewed gene: TMEM165: Rating: GREEN; Mode of pathogenicity: None; Publications: 22683087, 28323990, 27401145, 27008884, 26238249, 25609749; Phenotypes: Congenital disorder of glycosylation, type IIk, 614727 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1566 SPINT2 Cassandra Muller reviewed gene: SPINT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30445423, 19185281; Phenotypes: Diarrhea 3, secretory sodium, congenital, syndromic, 270420 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1566 SMPD1 Cassandra Muller reviewed gene: SMPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26499107; Phenotypes: Niemann-Pick disease, type A, 257200 (3), Niemann-Pick disease, type B, 607616 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1566 MCM4 Kate Scarff reviewed gene: MCM4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 22354167, 22354170, 22499342; Phenotypes: Immunodeficiency 54, MIM #609981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.1566 SLC25A13 Cassandra Muller edited their review of gene: SLC25A13: Changed rating: GREEN
Prepair 1000+ v1.1566 SLC6A8 Cassandra Muller reviewed gene: SLC6A8: Rating: GREEN; Mode of pathogenicity: None; Publications: 11326334, 11898126, 15154114, 17101918, 16086185; Phenotypes: Cerebral creatine deficiency syndrome 1, 300352 (3); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.1566 LTBP4 Kate Scarff reviewed gene: LTBP4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26866239, 22829427, 19836010; Phenotypes: Cutis laxa, autosomal recessive, type IC, #613177; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mosaic skin disorders v1.14 GNA13 Zornitza Stark Tag somatic tag was added to gene: GNA13.
Mendeliome v1.2351 GNA13 Zornitza Stark Tag somatic tag was added to gene: GNA13.
Intellectual disability syndromic and non-syndromic v1.78 DDX39B Zornitza Stark Marked gene: DDX39B as ready
Intellectual disability syndromic and non-syndromic v1.78 DDX39B Zornitza Stark Gene: ddx39b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v1.78 DDX39B Zornitza Stark Classified gene: DDX39B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v1.78 DDX39B Zornitza Stark Gene: ddx39b has been classified as Green List (High Evidence).
Genetic Epilepsy v1.117 DDX39B Zornitza Stark Marked gene: DDX39B as ready
Genetic Epilepsy v1.117 DDX39B Zornitza Stark Gene: ddx39b has been classified as Green List (High Evidence).
Genetic Epilepsy v1.117 DDX39B Zornitza Stark Classified gene: DDX39B as Green List (high evidence)
Genetic Epilepsy v1.117 DDX39B Zornitza Stark Gene: ddx39b has been classified as Green List (High Evidence).
Mendeliome v1.2351 DDX39B Zornitza Stark Marked gene: DDX39B as ready
Mendeliome v1.2351 DDX39B Zornitza Stark Gene: ddx39b has been classified as Green List (High Evidence).
Mendeliome v1.2351 DDX39B Zornitza Stark Classified gene: DDX39B as Green List (high evidence)
Mendeliome v1.2351 DDX39B Zornitza Stark Gene: ddx39b has been classified as Green List (High Evidence).
Microcephaly v1.301 CDO1 Zornitza Stark Marked gene: CDO1 as ready
Microcephaly v1.301 CDO1 Zornitza Stark Gene: cdo1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.301 CDO1 Zornitza Stark Classified gene: CDO1 as Amber List (moderate evidence)
Microcephaly v1.301 CDO1 Zornitza Stark Gene: cdo1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.300 CDO1 Zornitza Stark gene: CDO1 was added
gene: CDO1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: CDO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDO1 were set to 39949058
Phenotypes for gene: CDO1 were set to Syndromic disease, MONDO:0002254, CDO1-related
Review for gene: CDO1 was set to AMBER
Added comment: Three children with overlapping features including severe microcephaly and DD/ID. Three missense de novo variants were identified and were clustered around exon 3 and exon 4. The three missense variants identified p.(His147Arg, Ala131Val, Glu143Lys) are all absent from gnomAD v4.1.
Sources: Literature
Prepair 1000+ v1.1566 SLC52A3 Cassandra Muller reviewed gene: SLC52A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20206331, 26976849, 29053833, 25462087; Phenotypes: Brown-Vialetto-Van Laere syndrome 1, 211530 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v1.77 CDO1 Zornitza Stark Marked gene: CDO1 as ready
Intellectual disability syndromic and non-syndromic v1.77 CDO1 Zornitza Stark Gene: cdo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.77 CDO1 Zornitza Stark Classified gene: CDO1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v1.77 CDO1 Zornitza Stark Gene: cdo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.76 CDO1 Zornitza Stark gene: CDO1 was added
gene: CDO1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CDO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDO1 were set to 39949058
Phenotypes for gene: CDO1 were set to Syndromic disease, MONDO:0002254, CDO1-related
Review for gene: CDO1 was set to AMBER
Added comment: Three children with overlapping features including severe microcephaly and DD/ID. Three missense de novo variants were identified and were clustered around exon 3 and exon 4. The three missense variants identified p.(His147Arg, Ala131Val, Glu143Lys) are all absent from gnomAD v4.1.
Sources: Literature
Mendeliome v1.2350 CDO1 Zornitza Stark Marked gene: CDO1 as ready
Mendeliome v1.2350 CDO1 Zornitza Stark Gene: cdo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2350 CDO1 Zornitza Stark Phenotypes for gene: CDO1 were changed from Neurological Disorder MONDO:0100545 to Syndromic disease, MONDO:0002254, CDO1-related
Mendeliome v1.2349 CDO1 Zornitza Stark Classified gene: CDO1 as Amber List (moderate evidence)
Mendeliome v1.2349 CDO1 Zornitza Stark Gene: cdo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2348 CDO1 Zornitza Stark reviewed gene: CDO1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic disease, MONDO:0002254, CDO1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v1.75 PHACTR4 Zornitza Stark Marked gene: PHACTR4 as ready
Intellectual disability syndromic and non-syndromic v1.75 PHACTR4 Zornitza Stark Gene: phactr4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v1.75 PHACTR4 Zornitza Stark Classified gene: PHACTR4 as Amber List (moderate evidence)