ClinVar Genomic variation as it relates to human health
NM_004612.4(TGFBR1):c.52GCG[11] (p.Ala25_Ala26dup)
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.
Uncertain significance(3); Benign(1); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004612.4(TGFBR1):c.52GCG[11] (p.Ala25_Ala26dup)
Variation ID: 496264 Accession: VCV000496264.15
- Type and length
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Microsatellite, 6 bp
- Location
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Cytogenetic: 9q22.33 9: 99105255-99105256 (GRCh38) [ NCBI UCSC ] 9: 101867537-101867538 (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 17, 2018 May 1, 2024 Jan 13, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004612.4:c.52GCG[11] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004603.1:p.Ala25_Ala26dup inframe insertion NM_001130916.3:c.52GCG[11] NP_001124388.1:p.Ala25_Ala26dup inframe insertion NM_001306210.2:c.52GCG[11] NP_001293139.1:p.Ala25_Ala26dup inframe insertion NM_004612.2:c.73_78dup NC_000009.12:g.99105257GCG[11] NC_000009.11:g.101867539GCG[11] NG_007461.1:g.5128GCG[11] - Protein change
- Other names
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- Canonical SPDI
- NC_000009.12:99105255:GGCGGCGGCGGCGGCGGCGGCGGCGGCG:GGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
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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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0.05132 (GGCGGCGGCGGCGGCGGCG)
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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
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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 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
975 | 1052 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Mar 30, 2017 | RCV000590468.6 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 13, 2024 | RCV000704697.10 |
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
(Mar 30, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698485.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The TGFBR1 c.73_78dupGCGGCG (p.Ala25_Ala26dup) variant involves the duplication of six nucleotides in a repetitive region. One in silico tools predicts a deleterious outcome … (more)
Variant summary: The TGFBR1 c.73_78dupGCGGCG (p.Ala25_Ala26dup) variant involves the duplication of six nucleotides in a repetitive region. One in silico tools predicts a deleterious outcome for this variant. The frequency of this variant in population databases is not available due to lack of coverage or very low coverage of the chromosomal region. This variant was reported to be found in 1/2436 control chromosomes in the literature at a frequency of 0.0004105, which is approximately 263 times the estimated maximal expected allele frequency of a pathogenic TGFBR1 variant (0.0000016), suggesting this variant is possibly a benign polymorphism, although the allele number is very low. This variant has been reported in a sporadic BrC patient without evidence of causality. The variant of interest has not, to our knowledge, been reported in affected individuals via reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as VUS-possibly benign until more evidence becomes available. (less)
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Uncertain significance
(Jul 13, 2018)
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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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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV001333553.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
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Benign
(Sep 22, 2015)
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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: SCV001846179.1
First in ClinVar: Sep 10, 2021 Last updated: Sep 10, 2021 |
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Uncertain significance
(Jan 13, 2024)
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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: SCV000833655.6
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant, c.73_78dup, results in the insertion of 2 amino acid(s) of the TGFBR1 protein (p.Ala25_Ala26dup), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.73_78dup, results in the insertion of 2 amino acid(s) of the TGFBR1 protein (p.Ala25_Ala26dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TGFBR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 496264). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Likely benign
(Feb 21, 2023)
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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: SCV003861001.2
First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (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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TGFBR1(*)6A and Int7G24A variants of transforming growth factor-beta receptor 1 in Swedish familial and sporadic breast cancer. | Song B | British journal of cancer | 2007 | PMID: 17848956 |
Lack of an association between the TGFBR1*6A variant and colorectal cancer risk. | Skoglund J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2007 | PMID: 17575241 |
TGFBR1*6A is not associated with prostate cancer in men of European ancestry. | Suarez BK | Prostate cancer and prostatic diseases | 2005 | PMID: 15505640 |
The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer. | Samowitz WS | Gastroenterology | 2001 | PMID: 11606497 |
Text-mined citations for rs11466445 ...
HelpRecord last updated May 01, 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.