ClinVar Genomic variation as it relates to human health
NM_004612.4(TGFBR1):c.1442C>T (p.Ala481Val)
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_004612.4(TGFBR1):c.1442C>T (p.Ala481Val)
Variation ID: 1806277 Accession: VCV001806277.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q22.33 9: 99149235 (GRCh38) [ NCBI UCSC ] 9: 101911517 (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 24, 2022 Dec 24, 2022 Feb 2, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004612.4:c.1442C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004603.1:p.Ala481Val missense NM_001130916.3:c.1211C>T NP_001124388.1:p.Ala404Val missense NM_001306210.2:c.1454C>T NP_001293139.1:p.Ala485Val missense NM_001407416.1:c.1286C>T NP_001394345.1:p.Ala429Val missense NM_001407417.1:c.1274C>T NP_001394346.1:p.Ala425Val missense NM_001407418.1:c.1247C>T NP_001394347.1:p.Ala416Val missense NM_001407419.1:c.1247C>T NP_001394348.1:p.Ala416Val missense NM_001407420.1:c.1247C>T NP_001394349.1:p.Ala416Val missense NM_001407422.1:c.1247C>T NP_001394351.1:p.Ala416Val missense NM_001407423.1:c.1235C>T NP_001394352.1:p.Ala412Val missense NM_001407424.1:c.1235C>T NP_001394353.1:p.Ala412Val missense NM_001407425.1:c.1235C>T NP_001394354.1:p.Ala412Val missense NM_001407426.1:c.1235C>T NP_001394355.1:p.Ala412Val missense NM_001407427.1:c.1235C>T NP_001394356.1:p.Ala412Val missense NM_001407428.1:c.1235C>T NP_001394357.1:p.Ala412Val missense NM_001407429.1:c.1235C>T NP_001394358.1:p.Ala412Val missense NM_001407430.1:c.1235C>T NP_001394359.1:p.Ala412Val missense NM_001407432.1:c.1235C>T NP_001394361.1:p.Ala412Val missense NM_001407433.1:c.1235C>T NP_001394362.1:p.Ala412Val missense NM_001407434.1:c.1235C>T NP_001394363.1:p.Ala412Val missense NM_001407435.1:c.1211C>T NP_001394364.1:p.Ala404Val missense NM_001407436.1:c.1196C>T NP_001394365.1:p.Ala399Val missense NM_001407437.1:c.734C>T NP_001394366.1:p.Ala245Val missense NM_001407438.1:c.965C>T NP_001394367.1:p.Ala322Val missense NR_176360.1:n.1546C>T NR_176361.1:n.1651C>T NR_176362.1:n.1422C>T NR_176363.1:n.1410C>T NC_000009.12:g.99149235C>T NC_000009.11:g.101911517C>T NG_007461.1:g.49106C>T - Protein change
- A245V, A322V, A399V, A404V, A412V, A416V, A425V, A429V, A481V, A485V
- Other names
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- Canonical SPDI
- NC_000009.12:99149234: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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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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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TGFBR1 | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
920 | 997 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Feb 2, 2022 | RCV002470561.1 |
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
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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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Uncertain significance
(Feb 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Loeys-Dietz syndrome 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002768733.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as VUS – 3A. Following criteria are met: 0103 - Both loss- and gain-of-function are … (more)
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as VUS – 3A. Following criteria are met: 0103 - Both loss- and gain-of-function are known mechanisms of disease for this gene. Loss of function missense and NMD-predicted variants result in multiple self-healing squamous epithelioma, while gain of function missense cause Loeys-Dietz syndrome (OMIM, PMID: 21358634). (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from alanine to valine (exon 9). (N) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0502 - Missense variant with conflicting in silico predictions and/or uninformative conservation. (N) 0600 - Variant is located in an annotated domain or motif (catalytic protein kinase domain; PDB, NCBI). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0903 - Low evidence for segregation with disease, where this variant has been reported in this proband’s affected father and paternal aunt. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1206 - Variant is paternally inherited. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign (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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Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1. | Goudie DR | Nature genetics | 2011 | PMID: 21358634 |
Text-mined citations for this variant ...
HelpRecord last updated Mar 26, 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.