ClinVar Genomic variation as it relates to human health
NM_003242.6(TGFBR2):c.1178G>A (p.Cys393Tyr)
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.1178G>A (p.Cys393Tyr)
Variation ID: 264260 Accession: VCV000264260.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p24.1 3: 30672361 (GRCh38) [ NCBI UCSC ] 3: 30713853 (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 Dec 19, 2017 Feb 28, 2024 Mar 22, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003242.6:c.1178G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003233.4:p.Cys393Tyr missense NM_001024847.3:c.1253G>A NP_001020018.1:p.Cys418Tyr missense NM_001407126.1:c.1361G>A NP_001394055.1:p.Cys454Tyr missense NM_001407127.1:c.1286G>A NP_001394056.1:p.Cys429Tyr missense NM_001407128.1:c.1205G>A NP_001394057.1:p.Cys402Tyr missense NM_001407129.1:c.1181G>A NP_001394058.1:p.Cys394Tyr missense NM_001407130.1:c.1178G>A NP_001394059.1:p.Cys393Tyr missense NM_001407132.1:c.1073G>A NP_001394061.1:p.Cys358Tyr missense NM_001407133.1:c.1073G>A NP_001394062.1:p.Cys358Tyr missense NM_001407134.1:c.1073G>A NP_001394063.1:p.Cys358Tyr missense NM_001407135.1:c.1073G>A NP_001394064.1:p.Cys358Tyr missense NM_001407136.1:c.1073G>A NP_001394065.1:p.Cys358Tyr missense NM_001407137.1:c.893G>A NP_001394066.1:p.Cys298Tyr missense NM_001407138.1:c.818G>A NP_001394067.1:p.Cys273Tyr missense NC_000003.12:g.30672361G>A NC_000003.11:g.30713853G>A NG_007490.1:g.70860G>A LRG_779:g.70860G>A LRG_779t1:c.1253G>A LRG_779p1:p.Cys418Tyr LRG_779t2:c.1178G>A LRG_779p2:p.Cys393Tyr - Protein change
- C393Y, C418Y, C273Y, C358Y, C402Y, C429Y, C454Y, C298Y, C394Y
- Other names
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- Canonical SPDI
- NC_000003.12:30672360:G: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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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
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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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Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 22, 2022 | RCV000253481.6 |
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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Pathogenic
(Jul 06, 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: SCV000320065.4
First in ClinVar: Oct 03, 2016 Last updated: Nov 29, 2022 |
Comment:
The p.C393Y pathogenic mutation (also known as c.1178G>A), located in coding exon 4 of the TGFBR2 gene, results from a G to A substitution at … (more)
The p.C393Y pathogenic mutation (also known as c.1178G>A), located in coding exon 4 of the TGFBR2 gene, results from a G to A substitution at nucleotide position 1178. The cysteine at codon 393 is replaced by tyrosine, an amino acid with highly dissimilar properties, and is located in a protein kinase domain. This alteration was confirmed as de novo in a proband whose clinical presentation is consistent with Loeys-Dietz syndrome (LDS). Another alteration at the same codon, p.C393G (c.1177T>G), has been observed in an individual with LDS (Frischmeyer-Guerrerio PA et al. Sci Transl Med 2013; 5(195):195ra94) and in a thoracic aortic disease cohort (Jondeau G et al. Circ Cardiovasc Genet, 2016 Dec;9:548-558); however, clinical details were limited. Based on the supporting evidence, p.C393Y is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Mar 22, 2022)
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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: SCV002991592.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 2024 |
Comment:
This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein … (more)
This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 264260). This missense change has been observed in individual(s) with TGFBR2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 393 of the TGFBR2 protein (p.Cys393Tyr). (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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International Registry of Patients Carrying TGFBR1 or TGFBR2 Mutations: Results of the MAC (Montalcino Aortic Consortium). | Jondeau G | Circulation. Cardiovascular genetics | 2016 | PMID: 27879313 |
TGFβ receptor mutations impose a strong predisposition for human allergic disease. | Frischmeyer-Guerrerio PA | Science translational medicine | 2013 | PMID: 23884466 |
Text-mined citations for rs886039106 ...
HelpRecord last updated Feb 28, 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.