Thoracic aortic aneurysm and dissection

Gene: COL1A1

Red List (low evidence)

COL1A1 (collagen type I alpha 1 chain)
EnsemblGeneIds (GRCh38): ENSG00000108821
EnsemblGeneIds (GRCh37): ENSG00000108821
OMIM: 120150, Gene2Phenotype
COL1A1 is in 14 panels

9 reviews

Ivone Leong (Genomics England Curator)

Red List (low evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Red on this panel.
Created: 18 Nov 2019, 4:33 p.m. | Last Modified: 18 Nov 2019, 4:33 p.m.
Panel Version: 0.35

James Eden (Manchester)

Red List (low evidence)

Associated with OI, little association with aortopathy.
Created: 2 Oct 2019, 3:09 p.m. | Last Modified: 2 Oct 2019, 3:09 p.m.
Panel Version: 0.32

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Caffey disease 114000; Ehlers-Danlos syndrome, arthrochalasia type, 1 130060; Osteogenesis imperfecta, types I-IV

Publications

Alison Callaway (Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust)

I don't know

Present on Wessex aortopathy panel, pathogenic variants have been detected in patients referred with OI, but no pathogenic or likely pathogenic variants have been detected in patients referred specifically for aortopathy (without other COL1A1 specific syndromic features e.g. OI). Associated with EDS (arthrochalasia type) OMIM #130060 and OI (OMIM #166200,166210, 259420, 166220).
Created: 29 Aug 2019, 2:18 p.m. | Last Modified: 29 Aug 2019, 2:19 p.m.
Panel Version: 0.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice

Rebecca Whittington (South West GLH)

Red List (low evidence)

130060 AD Ehler's Danlos syndrome arthrochalasia type 1, which does not have a cardiac/aortopathy phenotype associated on OMIM; gene also causative of osteogeneisis imperfecta. Should this be included as it is similar situation to some of the red genes - involved in CTD but without aortopathy.
Created: 25 Mar 2019, 4:30 p.m.
Weerakkody et al 2016 Genet Med 18:1119 PMID:27011056 is one of several publications identifying variants in COL1A1 in EDS patients. One frameshift and two missense (affecting glycine in the G-X-Y collagen triple-helix motif) variants are described: c.1265delG: p.Gly422AlafsX119; c.643G>A: p.Gly215Ser; c.662G>C: p.Gly221Ala. None of these have any gnomAD frequency.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Nick Camm (NHS)

Green List (high evidence)

Rebecca Foulger (Genomics England curator)

PMID:26188975 perform WES in 102 TAAD patients using a 21-gene panel including COL1A1, COL1A2 and COL5A2: 2 patients had suspicious variants of unknown significance in COL1A1- V349F (previously reported in association with OI) and N1394S.
Created: 29 Jun 2017, 11:30 a.m.
COL1A1 is on this panel for syndromic TAAD: patients with syndromic thoracic aortic aneurysm suffer from conditions including Ehlers-Danlos syndrome (EDS). Osteogenesis Imperfecta (OI) patients can also present with TAAD as a secondary feature (PMID:10523481).
Created: 29 Jun 2017, 11:30 a.m.

Caroline Wright (Genomics England Curator)

Comment when marking as ready: Definite disease-causing gene, with phenotype overlapping Thoracic Aortic Aneurysm Disease
Created: 19 Feb 2016, 2:39 p.m.

Matina Prapa (Genomics England Curator)

Green List (high evidence)

Mice with a deletion in the first intron of the Col1a1 gene develop age-dependent aortic dissection and rupture (PMID: 14630726). Lower incidence of TAAD in humans harbouring COL1A1 mutations (PMID: 14630726)
Created: 12 Feb 2016, 11 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
#130000- Ehlers-Danlos syndrome, classic; #130060- Ehlers-Danlos syndrome, type VIIA

Publications

Ellen McDonagh (Genomics England Curator)

I don't know

Comment on list classification: Demoted from Amber to Red, after confirmation with the GMS Cardiology specialist disease group in a meeting in July 2019 that EDS genes should not be included, except vascular EDS (the COL3A1 should remain Green).
Created: 30 Aug 2019, 10:09 a.m. | Last Modified: 30 Aug 2019, 10:09 a.m.
Panel Version: 0.9
This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.
Created: 20 Feb 2019, 2:17 p.m.
Not on the Inherited Cardiac Condition Genes panel for Familial aortic anuerysm reported in: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10.​1007/​s12265-016-9673-5). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes.
Created: 19 Feb 2016, 10:54 a.m.
Comment on phenotypes: Sourced from OMIM
Created: 1 Feb 2016, 11:29 a.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • South West GLH
  • London South GLH
  • South West GLH
  • London South GLH
Phenotypes
  • Ehlers-Danlos syndrome, classic, 130000
  • Ehlers-Danlos syndrome, type VIIA, 130060
OMIM
120150
Clinvar variants
Variants in COL1A1
Penetrance
None
Panels with this gene

History Filter Activity

30 Aug 2019, Gel status: 1

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: col1a1 has been classified as Red List (Low Evidence).

30 Aug 2019, Gel status: 1

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: col1a1 has been classified as Red List (Low Evidence).

18 Apr 2019, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

gene: COL1A1 was added gene: COL1A1 was added to GMS FTAAD placeholder panel. Sources: Expert Review Amber,London South GLH,South West GLH Mode of inheritance for gene: COL1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: COL1A1 were set to Ehlers-Danlos syndrome, classic, 130000; Ehlers-Danlos syndrome, type VIIA, 130060