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Fetal anomalies

Gene: NOTCH3

Amber List (moderate evidence)
NOTCH3 (notch 3)
EnsemblGeneIds (GRCh38): ENSG00000074181
EnsemblGeneIds (GRCh37): ENSG00000074181
OMIM: 600276, Gene2Phenotype
NOTCH3 is in 17 panels

4 reviews

Ida Ertmanska (Genomics England Curator)

This gene and phenotype were reviewed during meetings in July and August 2026. The meetings included representatives of the North Thames and Central and South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler & Louise Carr (North Thames GLH), Sarah Graham & Elizabeth Young (Central & South GLH), and Alice Gardham, Esther Kinning, Vicki Harrison, Anna DeBurca, Natalie Canham, Sunayna Best, Soo-Mi Park & Tessa Homfray (R21 Clinical Oversight Group).
Created: 29 Oct 2026, 4:13 p.m. | Last Modified: 29 Oct 2026, 4:13 p.m.
Panel Version: 8.26
Created: 29 Oct 2026, 4:13 p.m.
Last Modified: 29 Oct 2026, 4:13 p.m.
Panel version: 8.26

Soo-Mi Park (CUHNFT)

Green List (high evidence)

MIM 621295. On multiple PanelApp panels for AD/AR disorders. Multiple reports (>>3) of biallelic loss-of-functio NOTCH3 variants, unlike the gain-of-function variants underlying CADASIL, associated with a distinct autosomal recessive leukodystrophy charactersed by congenital/early-onset arteriopathy with pyramidal signs, global developmental delay, epilepsy, visual impairment and white matter abnormalities (sometimes cavitating). Fetal MRI in 3rd trimester is capable of detecting white matter changes.
Created: 29 Oct 2026, 3:51 p.m. | Last Modified: 29 Oct 2026, 3:51 p.m.
Panel Version: 8.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, OMIM:621295; cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, MONDO:0979867

Publications

Created: 29 Oct 2026, 3:51 p.m.
Last Modified: 29 Oct 2026, 3:51 p.m.
Panel version: 8.25

Arina Puzriakova (Genomics England Curator)

This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Created: 10 Mar 2026, 11:35 a.m. | Last Modified: 10 Mar 2026, 11:35 a.m.
Panel Version: 6.148
Created: 10 Mar 2026, 11:35 a.m.
Last Modified: 10 Mar 2026, 11:35 a.m.
Panel version: 6.148

Esther Kinning (NHS Greater Glasgow and Clyde)

I don't know

Truncating variants in last exon leading to GOF and lateral meningocele syndrome- dysmorphism, cardiac, vertebral, skeletal connective tissue, motor delay, spinal meningoceles and chiari I malformation. One prenatal case with cystic hygroma, mild VM. No other antenatal reports. Variants in EGF domain cause CADASIL would be an incidental finding. One report of homozygous frameshift variant in a patient with global developmental delay, spastic tetraparesis, epilepsy, and bilateral periventricular white matter abnormalities (PMID: 41196431).
Created: 10 Mar 2026, 11:27 a.m. | Last Modified: 10 Mar 2026, 11:27 a.m.
Panel Version: 6.147

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Lateral meningocele syndrome, OMIM:130720

Publications

Created: 10 Mar 2026, 11:27 a.m.
Last Modified: 10 Mar 2026, 11:27 a.m.
Panel version: 6.147

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Amber
Phenotypes
  • Lateral meningocele syndrome, OMIM:130720
  • cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, MONDO:0979867
  • Cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, OMIM:621295
Tags
Q3_26_promote_green
OMIM
600276
Clinvar variants
Variants in NOTCH3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

2 Nov 2026, Gel status: 2

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q3_26_promote_green tag was added to gene: NOTCH3.

29 Oct 2026, Gel status: 2

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

Ida Ertmanska (Genomics England Curator)

Source NHS GMS was added to NOTCH3. Mode of inheritance for gene NOTCH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, OMIM:621295; cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, MONDO:0979867 for gene: NOTCH3 Publications for gene: NOTCH3 were updated from to 41196431; 38824264; 25870235; 37688971

10 Mar 2026, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Added phenotypes Lateral meningocele syndrome, OMIM:130720 for gene: NOTCH3

9 Mar 2026, Gel status: 2

Created, Added New Source, Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

gene: NOTCH3 was added gene: NOTCH3 was added to Fetal anomalies. Sources: Expert Review Amber Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted