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NM_000435.3(NOTCH3):c.2932A>C (p.Ser978Arg)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(1);Likely benign(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Sep 21, 2021)
Last evaluated:
May 11, 2020
Accession:
VCV000702452.6
Variation ID:
702452
Description:
single nucleotide variant
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NM_000435.3(NOTCH3):c.2932A>C (p.Ser978Arg)

Allele ID
694345
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.12
Genomic location
19: 15181023 (GRCh38) GRCh38 UCSC
19: 15291834 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000019.10:g.15181023T>G
NC_000019.9:g.15291834T>G
NG_009819.1:g.24959A>C
NM_000435.3:c.2932A>C MANE Select NP_000426.2:p.Ser978Arg missense
Protein change
S978R
Other names
-
Canonical SPDI
NC_000019.10:15181022:T:G
Functional consequence
-
Global minor allele frequency (GMAF)
0.00040 (G)

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00046
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00031
1000 Genomes Project 0.00040
The Genome Aggregation Database (gnomAD), exomes 0.00028
Trans-Omics for Precision Medicine (TOPMed) 0.00037
The Genome Aggregation Database (gnomAD) 0.00010
Links
dbSNP: rs141956294
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 3 criteria provided, single submitter Dec 31, 2019 RCV000871542.4
Uncertain significance 1 criteria provided, single submitter May 28, 2019 RCV000990177.1
Benign 1 criteria provided, single submitter May 11, 2020 RCV001288890.1
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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
835 854

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy type 1
Allele origin: unknown
Mendelics
Accession: SCV001141025.1
Submitted: (Oct 22, 2019)
Evidence details
Likely benign
(Dec 31, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Invitae
Accession: SCV001013219.2
Submitted: (Jan 29, 2020)
Evidence details
Benign
(May 11, 2020)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: unknown
Athena Diagnostics Inc
Accession: SCV001476289.1
Submitted: (Dec 30, 2020)
Evidence details
Publications
PubMed (2)
Likely benign
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799812.1
Submitted: (Aug 19, 2021)
Evidence details
Likely benign
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001968717.1
Submitted: (Sep 21, 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
A series of Notch3 mutations in CADASIL; insights from 3D molecular modelling and evolutionary analyses. Vlachakis D Journal of molecular biochemistry 2014 PMID: 31799216
Novel human pathological mutations. Gene symbol: NOTCH3. Disease: cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). Ferreira S Human genetics 2007 PMID: 17879447

Text-mined citations for rs141956294...

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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 Oct 21, 2021