ClinVar Genomic variation as it relates to human health
NM_001904.4(CTNNB1):c.1759C>T (p.Arg587Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001904.4(CTNNB1):c.1759C>T (p.Arg587Ter)
Variation ID: 423482 Accession: VCV000423482.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p22.1 3: 41235799 (GRCh38) [ NCBI UCSC ] 3: 41277290 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 27, 2017 Feb 7, 2023 Nov 3, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001904.4:c.1759C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001895.1:p.Arg587Ter nonsense NM_001098209.2:c.1759C>T NP_001091679.1:p.Arg587Ter nonsense NM_001098210.2:c.1759C>T NP_001091680.1:p.Arg587Ter nonsense NM_001330729.2:c.1738C>T NP_001317658.1:p.Arg580Ter nonsense NC_000003.12:g.41235799C>T NC_000003.11:g.41277290C>T NG_013302.2:g.41349C>T LRG_1108:g.41349C>T LRG_1108t1:c.1759C>T LRG_1108p1:p.Arg587Ter - Protein change
- R587*, R580*
- Other names
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- Canonical SPDI
- NC_000003.12:41235798:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CTNNB1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
384 | 748 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Jul 10, 2021 | RCV000486133.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 7, 2021 | RCV000624883.3 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Nov 3, 2022 | RCV001253207.4 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Mar 27, 2019)
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criteria provided, single submitter
Method: clinical testing
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Severe intellectual disability-progressive spastic diplegia syndrome
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001428810.1
First in ClinVar: Aug 16, 2020 Last updated: Aug 16, 2020 |
Number of individuals with the variant: 1
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Pathogenic
(Jul 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000573186.4
First in ClinVar: Apr 27, 2017 Last updated: Sep 24, 2021 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28856709, 27535533) (less)
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Pathogenic
(Nov 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Severe intellectual disability-progressive spastic diplegia syndrome
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002588788.1
First in ClinVar: Nov 05, 2022 Last updated: Nov 05, 2022 |
Comment:
The c.1759C>T;p.(Arg587*) variant creates a premature translational stop signal in the CTNNB1 gene. It is expected to result in an absent or disrupted protein product … (more)
The c.1759C>T;p.(Arg587*) variant creates a premature translational stop signal in the CTNNB1 gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 423482; PMID: 28856709) - PS4. This variant is not present in population databases (rs1064796453, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
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Pathogenic
(Jan 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000741916.4
First in ClinVar: Apr 15, 2018 Last updated: Feb 07, 2023 |
Comment:
The c.1759C>T (p.R587*) alteration, located in exon 11 (coding exon 10) of the CTNNB1 gene, consists of a C to T substitution at nucleotide position … (more)
The c.1759C>T (p.R587*) alteration, located in exon 11 (coding exon 10) of the CTNNB1 gene, consists of a C to T substitution at nucleotide position 1759. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 587. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from the Genome Aggregation Database (gnomAD), the CTNNB1 c.1759C>T alteration was not observed, with coverage at this position. This alteration has been determined to be the result of a de novo mutation in two individuals with phenotypes consistent with CTNNB1-related neurodevelopmental disorder (internal data); however, the possibility for germline mosaicism cannot be ruled out. In addition, this alteration was reported de novo in a patient who met criteria for atypical Rett syndrome (Yoo, 2017). Based on the available evidence, this alteration is classified as pathogenic. (less)
Number of individuals with the variant: 1
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Pathogenic
(Aug 18, 2017)
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no assertion criteria provided
Method: provider interpretation
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Severe intellectual disability-progressive spastic diplegia syndrome
Affected status: yes
Allele origin:
de novo
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GenomeConnect - Simons Searchlight
Accession: SCV001443350.1
First in ClinVar: Nov 21, 2020 Last updated: Nov 21, 2020 |
Comment:
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2017-08-18 and interpreted as Pathogenic. Variant was initially … (more)
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2017-08-18 and interpreted as Pathogenic. Variant was initially reported on 2016-11-29 by GTR ID of laboratory name 61756. The reporting laboratory might also submit to ClinVar. (less)
Sex: female
Testing laboratory: Ambry Genetics
Date variant was reported to submitter: 2016-11-29
Testing laboratory interpretation: Pathogenic
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Severe intellectual disability-progressive spastic diplegia syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Génétique des Maladies du Développement, Hospices Civils de Lyon
Accession: SCV001519039.1
First in ClinVar: Mar 18, 2021 Last updated: Mar 18, 2021 |
Sex: male
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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GABBR2 mutations determine phenotype in rett syndrome and epileptic encephalopathy. | Yoo Y | Annals of neurology | 2017 | PMID: 28856709 |
Text-mined citations for rs1064796453 ...
HelpRecord last updated Aug 06, 2023
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.