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NM_000435.3(NOTCH3):c.1819C>T (p.Arg607Cys)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Jul 4, 2021)
Last evaluated:
Oct 15, 2019
Accession:
VCV000374637.9
Variation ID:
374637
Description:
single nucleotide variant
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NM_000435.3(NOTCH3):c.1819C>T (p.Arg607Cys)

Allele ID
361523
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.12
Genomic location
19: 15187126 (GRCh38) GRCh38 UCSC
19: 15297937 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000019.10:g.15187126G>A
NC_000019.9:g.15297937G>A
NM_000435.3:c.1819C>T MANE Select NP_000426.2:p.Arg607Cys missense
NG_009819.1:g.18856C>T
Protein change
R607C
Other names
-
Canonical SPDI
NC_000019.10:15187125:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA9263542
dbSNP: rs777751303
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Oct 1, 2019 RCV000415985.5
Likely pathogenic 1 criteria provided, single submitter Oct 31, 2018 RCV000763036.1
Likely pathogenic 1 criteria provided, single submitter Oct 15, 2019 RCV001287012.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
NOTCH3 - - GRCh38
GRCh37
794 813

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy type 1
Lateral meningocele syndrome
Infantile myofibromatosis 2
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000893513.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Pathogenic
(Jun 12, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV000614242.3
Submitted: (Sep 25, 2019)
Evidence details
Publications
PubMed (9)
Comment:
The variant disrupts a cysteine residue in an EGF-like repeat domain, which are important for the structure of this protein. Therefore it is expected to … (more)
Likely pathogenic
(Oct 15, 2019)
criteria provided, single submitter
Method: clinical testing
none provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV001473650.1
Submitted: (Dec 11, 2020)
Evidence details
Comment:
The NOTCH3 c.1819C>T; p.Arg607Cys variant (rs777751303), also known as 1897C>T; R607C, is reported in the literature in multiple individuals and families affected with CADASIL (Dotti … (more)
Pathogenic
(Oct 01, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV000493485.12
Submitted: (Jul 04, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Primary involvement of neurovascular coupling in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Jokumsen-Cabral A Journal of neurology 2019 PMID: 31028544
The CADASIL Scale-J, A Modified Scale to Prioritize Access to Genetic Testing for Japanese CADASIL-Suspected Patients. Koizumi T Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 2019 PMID: 30956055
The role of clinical and neuroimaging features in the diagnosis of CADASIL. Bersano A Journal of neurology 2018 PMID: 30311053
New diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy in Japan. Mizuta I Journal of the neurological sciences 2017 PMID: 28991717
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
An unusual case of elderly-onset cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with multiple cerebrovascular risk factors. Watanabe M Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 2012 PMID: 20851625
The spectrum of Notch3 mutations in 28 Italian CADASIL families. Dotti MT Journal of neurology, neurosurgery, and psychiatry 2005 PMID: 15834039
The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. Singhal S Brain : a journal of neurology 2004 PMID: 15229130
Diagnostic strategies in CADASIL. Razvi SS Neurology 2003 PMID: 12821764
Evaluation of DHPLC analysis in mutational scanning of Notch3, a gene with a high G-C content. Escary JL Human mutation 2000 PMID: 11102981

Text-mined citations for rs777751303...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 10, 2021