Fetal anomalies
Gene: COL1A1
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: include on the Fetal anomalies panel as a Green gene.Created: 29 Apr 2019, 12:28 p.m.
Additional evidence from PMID:30266093: AD/de novo het variant identified in COL1A1 from fetal exome sequencing in Normand et al., 2018 (Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder, PMID:30266093).Created: 18 Apr 2019, 3:55 p.m.
Additional evidence from PMID:29595812:Variants identified in COL1A1 from fetal exome sequencing in Chandler et al., 2018 (Rapid diagnosis of fetal skeletal dysplasia using targeted exome sequencing, PMID:29595812). In one case, the variant is reported as a paternally-inherited VUS where no molecular diagnosis was made. In three cases the variants were De novo.Created: 18 Apr 2019, 3:54 p.m.
Additional evidence from PAGE study: Diagnostic Heterozygous varianst identified in COL1A1 from fetalexome sequencing inLord et al., 2019 (PMID:30712880).Created: 18 Apr 2019, 3:51 p.m.
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene. Additional notes from clinical review: Need caution when reviewing variants in COL1A1, because different variants are associated with different phenotypes. Gain of function variants cause a more severe phenotype than LOF variants, which cause a mild phenotype.Created: 24 Mar 2019, 4:30 p.m.
DDG2P rating in original PAGE list: Confirmed for EHLERS-DANLOS SYNDROME TYPE VIIA, Confirmed for OSTEOGENESIS IMPERFECTA TYPE I, Confirmed for OSTEOGENESIS IMPERFECTA TYPE III, Confirmed for EHLERS-DANLOS SYNDROME, CLASSIC TYPE, COL1A1-RELATED, Confirmed for CAFFEY DISEASE, Confirmed for OSTEOGENESIS IMPERFECTA TYPE IIA and Confirmed for COL1A1/2-RELATED OSTEOGENESIS IMPERFECTA.Created: 11 Dec 2018, 9:04 a.m.
In the original PAGE file, MOP listed as Dominant negative for EHLERS-DANLOS SYNDROME TYPE VIIA, OSTEOGENESIS IMPERFECTA TYPE I, OSTEOGENESIS IMPERFECTA TYPE III, OSTEOGENESIS IMPERFECTA TYPE IIA, COL1A1/2-RELATED OSTEOGENESIS IMPERFECTA and EHLERS-DANLOS SYNDROME, CLASSIC TYPE, COL1A1-RELATED. MOP listed as Uncertain for CAFFEY DISEASE.Created: 8 Nov 2018, 4:45 p.m.
Publications
Mode of pathogenicity
Other - please provide details in the comments
Added phenotypes COL1A1/2-RELATED OSTEOGENESIS IMPERFECTA for gene: COL1A1
Added phenotypes OSTEOGENESIS IMPERFECTA TYPE IIA for gene: COL1A1
Added phenotypes CAFFEY DISEASE for gene: COL1A1
Added phenotypes EHLERS-DANLOS SYNDROME, CLASSIC TYPE, COL1A1-RELATED for gene: COL1A1
Added phenotypes OSTEOGENESIS IMPERFECTA TYPE III for gene: COL1A1
Added phenotypes OSTEOGENESIS IMPERFECTA TYPE I for gene: COL1A1
Added phenotypes EHLERS-DANLOS SYNDROME TYPE VIIA for gene: COL1A1
gene: COL1A1 was added gene: COL1A1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: COL1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: COL1A1 were set to EHLERS-DANLOS SYNDROME TYPE VIIA