Thoracic aortic aneurysm or dissection

Gene: COL1A2

After consulting with the Genomics England Clinical Team, it was decided that this gene should remain Green on this panel.

Created: 13 Jan 2020, 10:40 a.m. | Last Modified: 13 Jan 2020, 10:40 a.m.

Panel Version: 1.110

MOI was corrected.

Created: 30 Sep 2019, 10:49 a.m. | Last Modified: 30 Sep 2019, 10:49 a.m.

Panel Version: 1.96

Red List (low evidence)

Gene not currently tested on Manchester cardiac gene panel. 566 variants listed on HGMD (accessed 24/09/2019). Very little literature showing aortic involvement.

Created: 24 Sep 2019, 1:55 p.m. | Last Modified: 24 Sep 2019, 1:56 p.m.

Panel Version: 1.93

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

Phenotypes
Ehlers-Danlos syndrome, arthrochalasia type, 2 617821; Ehlers-Danlos syndrome, cardiac valvular type 225320; Osteogenesis imperfecta, types II, III, IV 166210 259420 166220

I don't know

On Wessex aortopathy panel; to date, no pathogenic or likely pathogenic variants have been detected in cases referred for this panel.
Associated with EDS and OI, which overlap with TAAD

Created: 8 May 2019, 1:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Red List (low evidence)

617821 AD Ehlers-Danlos syndrome, arthrochalasia type - no cardiac involvement; 225320 AR Ehlers-Danlos syndrome, cardiac valvular type - aortic/mitral valve insufficiency

Created: 25 Mar 2019, 4:30 p.m.

Schwarze et al 2004 Am J Hum Genet 74:917 PMID:15077201 identified truncating variants - splice variants affecting +/-1 position (compound heterozygous) and nonsense (homozygous) that lead to disease through NMD.

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Green List (high evidence)

COL1A2 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, 11:35 a.m.

Comment on mode of inheritance: AD on OMIM

Created: 19 Feb 2016, 2:48 p.m.

Comment when marking as ready: Definite disease-causing gene, with phenotype overlapping Thoracic Aortic Aneurysm Disease

Created: 19 Feb 2016, 2:40 p.m.

Green List (high evidence)

Borderline aortic root dilatations described in the valvular type of EDS.

Created: 12 Feb 2016, 11:14 a.m.

Phenotypes
#225320- Ehlers-Danlos syndrome, cardiac valvular form; #130060- Ehlers-Danlos syndrome, type VIIB

Publications

• PMID: 15077201
• 17211858
• 21593863

I don't know

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, 11:30 a.m.