Thoracic aortic aneurysm or dissection

Gene: SMAD3

Green List (high evidence)

SMAD3 (SMAD family member 3)
EnsemblGeneIds (GRCh38): ENSG00000166949
EnsemblGeneIds (GRCh37): ENSG00000166949
OMIM: 603109, Gene2Phenotype
SMAD3 is in 16 panels

7 reviews

Eleanor Williams (Genomics England Curator)

Note one case with homozygous variant reported:
PMID: 32935439 - Baskin et al 2020 - first report of a LDS patient with biallelic SMAD3 variants (affecting splice site). Proband had classic Loeys-Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected.
Created: 28 Jul 2021, 12:22 a.m. | Last Modified: 28 Jul 2021, 12:22 a.m.
Panel Version: 1.121

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

Green List (high evidence)

Well characterised aortopathy gene; present on Wessex aortopathy and TAAD panels.
Created: 8 May 2019, 12:32 p.m.

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

Rebecca Whittington (South West GLH)

Green List (high evidence)

613795 Loeys-Dietz syndrome; well characterised gene
Created: 25 Mar 2019, 4:30 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

James Eden (Manchester)

Green List (high evidence)

Gene currently tested on Manchester cardiac gene panel. 95 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: definitive association with TAAD, definitive association with aneurysm-osteoarthritis syndrome (accessed 29/01/2019).
Created: 14 Feb 2019, 1:38 p.m.

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

Phenotypes
Loeys Dietz syndrome, type 3 (613795)

Publications

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

David Parry (University of Edinburgh)

Green List (high evidence)

Nick Camm (NHS)

Green List (high evidence)

Ellen McDonagh (Genomics England Curator)

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.
On the Inherited Cardiac Condition Genes panel 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, and it is unclear from the publication whether this gene falls into the disease-causing category. No. of mutations indicated in supplemental table = 9.
Created: 19 Feb 2016, 10:50 a.m.

Publications

  • doi:10.​1007/​s12265-016-9673-5
  • 21217753

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • South West GLH
  • London South GLH
  • North West GLH
  • Expert Review Green
  • Expert list
  • Emory Genetics Laboratory
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Loeys Dietz syndrome, type 3, 613795
  • Loeys Dietz syndrome, type 3 (613795)
OMIM
603109
Clinvar variants
Variants in SMAD3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

21 Feb 2019, Gel status: 4

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to SMAD3. Mode of inheritance for gene SMAD3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to SMAD3.

14 Feb 2019, Gel status: 3

Added New Source, Set Phenotypes, Set publications, Status Update

Ellen McDonagh (Genomics England Curator)

Source North West GLH was added to SMAD3. Added phenotypes Loeys Dietz syndrome, type 3 (613795) for gene: SMAD3 Publications for gene SMAD3 were changed from to 21217753; 29392890 Rating Changed from Green List (high evidence) to Green List (high evidence)

19 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Caroline Wright (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

3 Jul 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SMAD3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

3 Jul 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

SMAD3 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN,Emory Genetics Laboratory,Expert list

3 Jul 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SMAD3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

3 Jul 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

SMAD3 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN,Emory Genetics Laboratory,Expert list

3 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SMAD3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

3 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SMAD3 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN,Emory Genetics Laboratory,Expert list

3 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SMAD3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

3 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

SMAD3 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN,Emory Genetics Laboratory,Expert list

3 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SMAD3 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN,Emory Genetics Laboratory,Expert list