Fetal anomalies
Gene: THSD1

THSD1 (thrombospondin type 1 domain containing 1)
EnsemblGeneIds (GRCh38): ENSG00000136114
EnsemblGeneIds (GRCh37): ENSG00000136114
OMIM: 616821, Gene2Phenotype
THSD1 is in 2 panels

4 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 25 Feb 2025, 11:15 a.m. | Last Modified: 25 Feb 2025, 11:15 a.m.

Panel Version: 5.78

This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Created: 20 Feb 2025, 9:40 p.m. | Last Modified: 20 Feb 2025, 9:40 p.m.

Panel Version: 5.16

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 20 Feb 2025, 9:40 p.m.
Last Modified: 20 Feb 2025, 9:40 p.m.
Panel version: 5.78

Sunayna Best (Leeds Teaching Hospitals NHS Trust)

Green List (high evidence)

Not on any PanelApp panels. Multiple case reports with consistent prenatal phenotype (hydrops, congenital heart disease, lymphoedema). Can't find any functional evidence.
Created: 20 Feb 2025, 9:35 p.m. | Last Modified: 20 Feb 2025, 9:35 p.m.

Panel Version: 5.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Lymphatic malformation 13, MIM#620244

Publications

Created: 20 Feb 2025, 9:35 p.m.
Last Modified: 20 Feb 2025, 9:35 p.m.
Panel version: 5.15

Arina Puzriakova (Genomics England Curator)

Comment on list classification: New gene added to this panel by Rhiannon Mellis (GOSH). Rating Amber inline with this review, awaiting further evidence supporting that this gene can cause a fetal phenotype.
Created: 22 Aug 2022, 4:17 p.m. | Last Modified: 22 Aug 2022, 4:17 p.m.

Panel Version: 1.959

Created: 22 Aug 2022, 4:17 p.m.
Last Modified: 22 Aug 2022, 4:17 p.m.
Panel version: 1.959

Rhiannon Mellis (Great Ormond Street Hospital)

I don't know

This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.

Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).

Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene pending more evidence.

Details of review:
Not currently Green on any panels. Amber on Cerebral vascular malformations. (Heterozygous mutations identified in nine families with intracerebral aneurysms plus animal models but unclear on penetrance.)

Shamseldin et al 2018 (PMID: 28749478) report a fetal case with hydrops and a HOMOZYGOUS likely pathogenic variant in THSD1. The same group previously identified this same founder mutation in THSD1 in another 3 families with hydrops/oedema (PMID: 26036949)
Sources: Expert Review, Literature
Created: 11 Aug 2022, 1:05 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intracerebral aneurysms; ?Hydrops fetalis

Publications

PMID: 28749478
26036949

Created: 11 Aug 2022, 1:05 p.m.

Panel version: 1.900

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
NHS GMS

Phenotypes

Lymphatic malformation 13, OMIM:620244

OMIM

616821

Clinvar variants

Variants in THSD1

Penetrance

None

Publications

Panels with this gene