Fetal anomalies
Gene: COL1A1

COL1A1 (collagen type I alpha 1 chain)
EnsemblGeneIds (GRCh38): ENSG00000108821
EnsemblGeneIds (GRCh37): ENSG00000108821
OMIM: 120150, Gene2Phenotype
COL1A1 is in 12 panels

1 review

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

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

30266093

Mode of pathogenicity
Other - please provide details in the comments

Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.222

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

PAGE DD-Gene2Phenotype
Expert Review Green

Phenotypes

COL1A1/2-RELATED OSTEOGENESIS IMPERFECTA
EHLERS-DANLOS SYNDROME, CLASSIC TYPE, COL1A1-RELATED
OSTEOGENESIS IMPERFECTA TYPE III
EHLERS-DANLOS SYNDROME TYPE VIIA
OSTEOGENESIS IMPERFECTA TYPE IIA
CAFFEY DISEASE
OSTEOGENESIS IMPERFECTA TYPE I

OMIM

120150

Clinvar variants

Variants in COL1A1

Penetrance

None

Panels with this gene