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NM_000435.3(NOTCH3):c.1927T>G (p.Cys643Gly) AND Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 3, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003238175.1

Allele description [Variation Report for NM_000435.3(NOTCH3):c.1927T>G (p.Cys643Gly)]

NM_000435.3(NOTCH3):c.1927T>G (p.Cys643Gly)

Gene:
NOTCH3:notch receptor 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.12
Genomic location:
Preferred name:
NM_000435.3(NOTCH3):c.1927T>G (p.Cys643Gly)
HGVS:
  • NC_000019.10:g.15186902A>C
  • NG_009819.1:g.19080T>G
  • NM_000435.3:c.1927T>GMANE SELECT
  • NP_000426.2:p.Cys643Gly
  • NC_000019.9:g.15297713A>C
Protein change:
C643G
Molecular consequence:
  • NM_000435.3:c.1927T>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1
Synonyms:
Dementia, hereditary multi-infarct type; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1
Identifiers:
MONDO: MONDO:0000914; MedGen: C4551768; Orphanet: 136; OMIM: 125310

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003936097Institute of Human Genetics, University of Goettingen
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jul 3, 2023) 		unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknown1not providednot providednot providednot providedclinical testing

Citations

PubMed

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, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Institute of Human Genetics, University of Goettingen, SCV003936097.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testing PubMed (1)

Description

The variant c.1927T>G (p.(Cys643Gly)) in exon 12 of the NOTCH3-gene is not found in the gnomAD database, it affects a highly conserved nucleotide and a highly conserved amino acid within a protein domain and there is a large physicochemical difference between Cys and Gly. This variant has a pathogenic computational verdict based on in silico prediction algorithms. ACMG criteria used for classification: PM2_mod, PP2, PP3.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Jul 8, 2023