Intellectual disability syndromic and non-syndromic
Gene: NOTCH3

NOTCH3 (notch 3)
EnsemblGeneIds (GRCh38): ENSG00000074181
EnsemblGeneIds (GRCh37): ENSG00000074181
OMIM: 600276, Gene2Phenotype
NOTCH3 is in 13 panels

2 reviews

Ain Roesley (Victorian Clinical Genetics Services)

Green List (high evidence)

Pre-print (https://sciprofiles.com/publication/view/62eb776390415f0166f73fae7cd172ed)

Review of research and diagnostic databases and literature review found 50 individuals from 31 families with biallelic variants.

13 PTCS (including splice) and 15 missense resulting in gain or loss of Cys residue.

AR PTCs are associated with early onset leukoencephalopathy including cognitive decline, dev delay/ID and dysmorphism; seizures, spasticity, hypotonia, ataxia

AR missense are associated with CADASIL-like phenotype
Created: 30 Apr 2024, 4:51 a.m. | Last Modified: 30 Apr 2024, 4:51 a.m.

Panel Version: 0.5790

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder MONDO:0700092, NOTCH3-related

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

Created: 30 Apr 2024, 4:51 a.m.
Last Modified: 30 Apr 2024, 4:51 a.m.
Panel version: 0.5790

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Red List (low evidence)

Progressive neurological disorder rather than ID.
Created: 7 Dec 2019, 9:03 p.m. | Last Modified: 7 Dec 2019, 9:03 p.m.

Panel Version: 0.874

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310

Created: 7 Dec 2019, 9:03 p.m.
Last Modified: 7 Dec 2019, 9:03 p.m.
Panel version: 0.874

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Genetic Health Queensland

Phenotypes

neurodevelopmental disorder MONDO:0700092, NOTCH3-related
Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310

OMIM

600276

Clinvar variants

Variants in NOTCH3

Penetrance

None

Panels with this gene

History Filter Activity

30 Apr 2024, Gel status: 3

Set Phenotypes

Ain Roesley (Victorian Clinical Genetics Services)

Phenotypes for gene: NOTCH3 were changed from neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310

30 Apr 2024, Gel status: 3

Set Phenotypes

Ain Roesley (Victorian Clinical Genetics Services)

Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310

30 Apr 2024, Gel status: 3

Set mode of inheritance

Ain Roesley (Victorian Clinical Genetics Services)

Mode of inheritance for gene: NOTCH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal

30 Apr 2024, Gel status: 3

Entity classified by Genomics England curator

Ain Roesley (Victorian Clinical Genetics Services)

Gene: notch3 has been classified as Green List (High Evidence).

7 Dec 2019, Gel status: 1