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Genetic Epilepsy

Gene: NOTCH3

Green List (high evidence)

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, 5:02 a.m. | Last Modified: 30 Apr 2024, 5:02 a.m.
Panel Version: 0.2611

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

Krithika Murali (Victorian Clinical Genetics Services)

Red List (low evidence)

CADASIL typically presents with adult-onset migraine, TIA/stroke, cognitive disorders. Seizures noted in 5-10% of patients with CADASIL, usually preceded by stroke. Less than 5 cases described of adult-onset epilepsy as initial presenting symptom of CADASIL. All had characteristic MRI-B changes and review of cases shows that a number of them had preceding migraine or other symptoms.

Not suitable for inclusion in genetic epilepsy panel as seizures are adult-onset, rarely observed, and usually develop as a secondary phenomenon.
Sources: Expert list, Literature
Created: 17 Oct 2021, 11:50 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
?Myofibromatosis, infantile 2 - 615293; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310; Lateral meningocele syndrome - 130720

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
  • Expert list
Phenotypes
  • neurodevelopmental disorder MONDO:0700092, NOTCH3-related
  • Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310
OMIM
600276
Clinvar variants
Variants in NOTCH3
Penetrance
None
Publications
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 - 125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 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 - 125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 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).

18 Oct 2021, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: notch3 has been classified as Red List (Low Evidence).

18 Oct 2021, Gel status: 1

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: NOTCH3 were changed from ?Myofibromatosis, infantile 2 - 615293; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310; Lateral meningocele syndrome - 130720 to Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310

18 Oct 2021, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: notch3 has been classified as Red List (Low Evidence).

17 Oct 2021, Gel status: 0

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

Krithika Murali (Victorian Clinical Genetics Services)

gene: NOTCH3 was added gene: NOTCH3 was added to Genetic Epilepsy. Sources: Expert list,Literature Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NOTCH3 were set to 33020014; 30776699; 21414809; 30056822; 17675836 Phenotypes for gene: NOTCH3 were set to ?Myofibromatosis, infantile 2 - 615293; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 - 125310; Lateral meningocele syndrome - 130720 Review for gene: NOTCH3 was set to RED