ClinVar Genomic variation as it relates to human health
NM_003242.6(TGFBR2):c.1378C>G (p.Arg460Gly)
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.1378C>G (p.Arg460Gly)
Variation ID: 1470300 Accession: VCV001470300.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p24.1 3: 30674228 (GRCh38) [ NCBI UCSC ] 3: 30715720 (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 Mar 28, 2022 Feb 28, 2024 Jan 12, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003242.6:c.1378C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003233.4:p.Arg460Gly missense NM_001024847.3:c.1453C>G NP_001020018.1:p.Arg485Gly missense NM_001407126.1:c.1561C>G NP_001394055.1:p.Arg521Gly missense NM_001407127.1:c.1486C>G NP_001394056.1:p.Arg496Gly missense NM_001407128.1:c.1405C>G NP_001394057.1:p.Arg469Gly missense NM_001407129.1:c.1381C>G NP_001394058.1:p.Arg461Gly missense NM_001407130.1:c.1378C>G NP_001394059.1:p.Arg460Gly missense NM_001407132.1:c.1273C>G NP_001394061.1:p.Arg425Gly missense NM_001407133.1:c.1273C>G NP_001394062.1:p.Arg425Gly missense NM_001407134.1:c.1273C>G NP_001394063.1:p.Arg425Gly missense NM_001407135.1:c.1273C>G NP_001394064.1:p.Arg425Gly missense NM_001407136.1:c.1273C>G NP_001394065.1:p.Arg425Gly missense NM_001407137.1:c.1093C>G NP_001394066.1:p.Arg365Gly missense NM_001407138.1:c.1018C>G NP_001394067.1:p.Arg340Gly missense NC_000003.12:g.30674228C>G NC_000003.11:g.30715720C>G NG_007490.1:g.72727C>G LRG_779:g.72727C>G LRG_779t1:c.1453C>G LRG_779p1:p.Arg485Gly LRG_779t2:c.1378C>G LRG_779p2:p.Arg460Gly - Protein change
- R485G, R460G, R340G, R496G, R425G, R469G, R521G, R461G, R365G
- Other names
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- Canonical SPDI
- NC_000003.12:30674227:C:G
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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 |
1068 | 1093 |
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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Jan 12, 2021 | RCV001995183.6 |
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
(Jan 12, 2021)
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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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Invitae
Accession: SCV002252516.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has … (more)
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg460 amino acid residue in TGFBR2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16027248, 16885183, 25644172, 27508510, 23884466, 18852674, 21098638). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TGFBR2 protein function. This variant has been observed in individual(s) with clinical features of TGFBR2-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 460 of the TGFBR2 protein (p.Arg460Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. (less)
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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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Increased Prevalence of Inflammatory Bowel Disease in Patients with Mutations in Genes Encoding the Receptor Subunits for TGFβ. | Guerrerio AL | Inflammatory bowel diseases | 2016 | PMID: 27508510 |
Gene panel sequencing in heritable thoracic aortic disorders and related entities - results of comprehensive testing in a cohort of 264 patients. | Campens L | Orphanet journal of rare diseases | 2015 | PMID: 25644172 |
TGFβ receptor mutations impose a strong predisposition for human allergic disease. | Frischmeyer-Guerrerio PA | Science translational medicine | 2013 | PMID: 23884466 |
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 |
Histopathologic findings in ascending aortas from individuals with Loeys-Dietz syndrome (LDS). | Maleszewski JJ | The American journal of surgical pathology | 2009 | PMID: 18852674 |
Clinical features in a family with an R460H mutation in transforming growth factor beta receptor 2 gene. | Law C | Journal of medical genetics | 2006 | PMID: 16885183 |
Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections. | Pannu H | Circulation | 2005 | PMID: 16027248 |
Text-mined citations for rs104893811 ...
HelpRecord last updated Mar 05, 2024
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.