ClinVar Genomic variation as it relates to human health
NM_003242.6(TGFBR2):c.1599T>A (p.Cys533Ter)
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_003242.6(TGFBR2):c.1599T>A (p.Cys533Ter)
Variation ID: 1776068 Accession: VCV001776068.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p24.1 3: 30691494 (GRCh38) [ NCBI UCSC ] 3: 30732986 (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 Nov 29, 2022 Nov 29, 2022 Jun 12, 2017 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003242.6:c.1599T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003233.4:p.Cys533Ter nonsense NM_001024847.3:c.1674T>A NP_001020018.1:p.Cys558Ter nonsense NM_001407126.1:c.1782T>A NP_001394055.1:p.Cys594Ter nonsense NM_001407127.1:c.1707T>A NP_001394056.1:p.Cys569Ter nonsense NM_001407128.1:c.1626T>A NP_001394057.1:p.Cys542Ter nonsense NM_001407129.1:c.1602T>A NP_001394058.1:p.Cys534Ter nonsense NM_001407130.1:c.1596T>A NP_001394059.1:p.Cys532Ter nonsense NM_001407132.1:c.1494T>A NP_001394061.1:p.Cys498Ter nonsense NM_001407133.1:c.1494T>A NP_001394062.1:p.Cys498Ter nonsense NM_001407134.1:c.1494T>A NP_001394063.1:p.Cys498Ter nonsense NM_001407135.1:c.1494T>A NP_001394064.1:p.Cys498Ter nonsense NM_001407136.1:c.1494T>A NP_001394065.1:p.Cys498Ter nonsense NM_001407137.1:c.1314T>A NP_001394066.1:p.Cys438Ter nonsense NM_001407138.1:c.1239T>A NP_001394067.1:p.Cys413Ter nonsense NM_001407139.1:c.729T>A NP_001394068.1:p.Cys243Ter nonsense NC_000003.12:g.30691494T>A NC_000003.11:g.30732986T>A NG_007490.1:g.89993T>A LRG_779:g.89993T>A LRG_779t1:c.1674T>A LRG_779p1:p.Cys558Ter LRG_779t2:c.1599T>A LRG_779p2:p.Cys533Ter - Protein change
- C534*, C594*, C243*, C533*, C438*, C532*, C558*, C413*, C498*, C542*, C569*
- Other names
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- Canonical SPDI
- NC_000003.12:30691493:T:A
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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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- Links
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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TGFBR2 | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1131 | 1156 |
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
Help
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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Likely pathogenic (1) |
criteria provided, single submitter
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Jun 12, 2017 | RCV002398585.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
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
Help
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
Help
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
(Jun 12, 2017)
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criteria provided, single submitter
Method: clinical testing
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Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002707290.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.C533* variant (also known as c.1599T>A), located in coding exon 7 of the TGFBR2 gene, results from a T to A substitution at nucleotide … (more)
The p.C533* variant (also known as c.1599T>A), located in coding exon 7 of the TGFBR2 gene, results from a T to A substitution at nucleotide position 1599. This changes the amino acid from a cysteine to a stop codon within coding exon 7. This stop codon occurs at the 3' terminus of TGFBR2 and is not expected to trigger nonsense-mediated decay. However, this variant eliminates the last 35 amino acids, including 12 amino acids in the protein kinase domain. Multiple nonsense and missense alterations in the C-terminal end of the kinase domain have been associated with Loeys-Dietz syndrome (LDS) or LDS-related phenotypes (e.g., p.R495*, p.W521*, p.C533R, p.C533F, p.C537R and p.C537P) (Loeys BL et al. N. Engl. J. Med. 2006;355:788-98; Stheneur C et al. Hum. Mutat. 2008;29:E284-95; Horbelt D et al. J. Cell. Sci. 2010;123:4340-50). Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
Number of individuals with the variant: 1
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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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Quantitative analysis of TGFBR2 mutations in Marfan-syndrome-related disorders suggests a correlation between phenotypic severity and Smad signaling activity. | Horbelt D | Journal of cell science | 2010 | PMID: 21098638 |
Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz syndrome and related disorders. | Stheneur C | Human mutation | 2008 | PMID: 18781618 |
Aneurysm syndromes caused by mutations in the TGF-beta receptor. | Loeys BL | The New England journal of medicine | 2006 | PMID: 16928994 |
Heterozygous TGFBR2 mutations in Marfan syndrome. | Mizuguchi T | Nature genetics | 2004 | PMID: 15235604 |
Missense mutations of the transforming growth factor beta type II receptor in human head and neck squamous carcinoma cells. | Garrigue-Antar L | Cancer research | 1995 | PMID: 7664267 |
Signaling activity of transforming growth factor beta type II receptors lacking specific domains in the cytoplasmic region. | Wieser R | Molecular and cellular biology | 1993 | PMID: 8246946 |
Text-mined citations for this variant ...
HelpRecord last updated Nov 29, 2022
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.