ClinVar Genomic variation as it relates to human health
NM_003242.6(TGFBR2):c.1159G>A (p.Val387Met)
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(4); Likely benign(11)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_003242.6(TGFBR2):c.1159G>A (p.Val387Met)
Variation ID: 44651 Accession: VCV000044651.82
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 3p24.1 3: 30672342 (GRCh38) [ NCBI UCSC ] 3: 30713834 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 6, 2014 Apr 15, 2024 Jan 31, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_003242.6:c.1159G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003233.4:p.Val387Met missense NM_001024847.3:c.1234G>A NP_001020018.1:p.Val412Met missense NM_001407126.1:c.1342G>A NP_001394055.1:p.Val448Met missense NM_001407127.1:c.1267G>A NP_001394056.1:p.Val423Met missense NM_001407128.1:c.1186G>A NP_001394057.1:p.Val396Met missense NM_001407129.1:c.1162G>A NP_001394058.1:p.Val388Met missense NM_001407130.1:c.1159G>A NP_001394059.1:p.Val387Met missense NM_001407132.1:c.1054G>A NP_001394061.1:p.Val352Met missense NM_001407133.1:c.1054G>A NP_001394062.1:p.Val352Met missense NM_001407134.1:c.1054G>A NP_001394063.1:p.Val352Met missense NM_001407135.1:c.1054G>A NP_001394064.1:p.Val352Met missense NM_001407136.1:c.1054G>A NP_001394065.1:p.Val352Met missense NM_001407137.1:c.874G>A NP_001394066.1:p.Val292Met missense NM_001407138.1:c.799G>A NP_001394067.1:p.Val267Met missense NC_000003.12:g.30672342G>A NC_000003.11:g.30713834G>A NG_007490.1:g.70841G>A LRG_779:g.70841G>A LRG_779t1:c.1234G>A LRG_779p1:p.Val412Met LRG_779t2:c.1159G>A LRG_779p2:p.Val387Met P37173:p.Val387Met - Protein change
- V387M, V412M, V267M, V423M, V448M, V396M, V352M, V292M, V388M
- Other names
- p.V387M:GTG>ATG
- Canonical SPDI
- NC_000003.12:30672341:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00020 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00020
1000 Genomes Project 30x 0.00031
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00231
Trans-Omics for Precision Medicine (TOPMed) 0.00106
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 | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
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. |
|||
TGFBR2 | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1131 | 1156 |
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 5, 2017 | RCV000037728.20 | |
Uncertain significance (1) |
no assertion criteria provided
|
Jun 1, 2014 | RCV000148893.10 | |
Conflicting interpretations of pathogenicity (6) |
criteria provided, conflicting classifications
|
Jan 31, 2024 | RCV000249404.32 | |
Likely benign (2) |
criteria provided, single submitter
|
Jun 14, 2016 | RCV000288248.15 | |
Benign (1) |
criteria provided, single submitter
|
May 28, 2019 | RCV000345619.11 | |
not provided (1) |
no classification provided
|
- | RCV000509502.9 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Sep 19, 2017 | RCV000768109.9 | |
Likely benign (1) |
criteria provided, single submitter
|
Mar 19, 2018 | RCV001094865.12 | |
Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Sep 1, 2023 | RCV001703884.25 | |
Benign (1) |
criteria provided, single submitter
|
Dec 11, 2020 | RCV002277125.10 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Mar 30, 2021 | RCV003224121.8 | |
Likely benign (1) |
criteria provided, single submitter
|
Jul 11, 2019 | RCV003904922.1 | |
click to load more click to collapse |
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
Help
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Nov 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: yes
Allele origin:
germline
|
Center for Human Genetics, Inc, Center for Human Genetics, Inc
Accession: SCV000782370.1
First in ClinVar: May 26, 2018 Last updated: May 26, 2018 |
|
|
Benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Marfan syndrome
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001136356.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
Benign
(Jan 15, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV001333525.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
|
|
Benign
(Dec 11, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Ehlers-Danlos syndrome
Affected status: unknown
Allele origin:
germline
|
Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002566150.1
First in ClinVar: Aug 29, 2022 Last updated: Aug 29, 2022 |
|
|
Likely benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000559156.9
First in ClinVar: Dec 06, 2016 Last updated: Feb 20, 2024 |
|
|
Likely benign
(Apr 18, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001159277.6
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
|
|
Likely benign
(Jul 11, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
TGFBR2-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004726282.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
Likely benign
(Sep 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002544777.10
First in ClinVar: Jul 09, 2022 Last updated: Apr 15, 2024 |
Comment:
TGFBR2: PP3, BS1
Number of individuals with the variant: 9
|
|
Likely benign
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Thoracic Aortic Aneurysms and Aortic Dissections
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000442882.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
Likely benign
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Loeys-Dietz Syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000442880.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
Uncertain significance
(Sep 19, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Colorectal cancer, hereditary nonpolyposis, type 6
Loeys-Dietz syndrome 2
Affected status: unknown
Allele origin:
germline
|
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV000899024.1
First in ClinVar: Apr 25, 2019 Last updated: Apr 25, 2019 |
Comment:
TGFBR2 NM_003242.5 exon 4 p.Val387Met (c.1234G>A): This variant has been reported in the literature in at least 1 individual with suspicion of a syndromic aortopathy; … (more)
TGFBR2 NM_003242.5 exon 4 p.Val387Met (c.1234G>A): This variant has been reported in the literature in at least 1 individual with suspicion of a syndromic aortopathy; however, the authors of this study suggested that this variant is likely benign (Lerner-Ellis 2014 PMID:24793577). In addition, this variant is present in 0.1% (251/125876) of European individuals, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs35766612). This variant is present in ClinVar (Variation ID:44651). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (less)
|
|
Likely benign
(Mar 16, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000902905.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
|
Benign
(Sep 05, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918310.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
|
|
Likely benign
(Apr 23, 2010)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061390.6
First in ClinVar: May 03, 2013 Last updated: Jun 02, 2019 |
Number of individuals with the variant: 2
|
|
Likely benign
(Mar 19, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Loeys-Dietz syndrome 2
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000442881.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Likely benign
(Aug 07, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000250935.7
First in ClinVar: Oct 11, 2015 Last updated: Apr 09, 2018 |
Comment:
This variant is associated with the following publications: (PMID: 32560555, 27879313, 26332594, 26017485, 24941995, 25116393, 16791849, 25637381, 18781618, 23074336, 16571647, 21524434, 17319955, 16928994, 11212236, 24055113)
|
|
Likely benign
(Jun 18, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Familial thoracic aortic aneurysm and aortic dissection
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000319520.4
First in ClinVar: Oct 02, 2016 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, … (more)
This alteration is classified as likely benign based on a combination of the following: 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)
Number of individuals with the variant: 1
|
|
Uncertain significance
(Mar 30, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Loeys-Dietz syndrome 2
Colorectal cancer, hereditary nonpolyposis, type 6 Malignant tumor of esophagus
Affected status: unknown
Allele origin:
germline
|
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV003920555.1
First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023 |
Comment:
TGFBR2 NM_003242 exon 4 p.Val387Met (c.1234G>A): This variant has been reported in the literature in at least 1 individual with suspicion of a syndromic aortopathy; … (more)
TGFBR2 NM_003242 exon 4 p.Val387Met (c.1234G>A): This variant has been reported in the literature in at least 1 individual with suspicion of a syndromic aortopathy; however, the authors of this study suggested that this variant is likely benign (Lerner-Ellis 2014 PMID:24793577). In addition, this variant is present in 0.1% (251/125876) of European individuals, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs35766612). This variant is present in ClinVar (Variation ID:44651). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (less)
|
|
Uncertain significance
(Jun 01, 2014)
|
no assertion criteria provided
Method: research
|
Aortic aneurysm, thoracic
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190639.1 First in ClinVar: Dec 06, 2014 Last updated: Dec 06, 2014 |
|
|
Uncertain significance
(May 17, 2016)
|
no assertion criteria provided
Method: clinical testing
|
Loeys-Dietz syndrome
Affected status: yes
Allele origin:
germline
|
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital
Accession: SCV000692265.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Thoracic aortic aneurysm
Thoracic aortic dissection Loeys-Dietz syndrome
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect, ClinGen
Accession: SCV000607367.1
First in ClinVar: Oct 16, 2017 Last updated: Oct 16, 2017 |
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical … (more)
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Myopia (present) , Memory impairment (present) , Generalized hypotonia (present) , Abnormality of coordination (present) , Cognitive impairment (present) , Short attention span (present) , … (more)
Myopia (present) , Memory impairment (present) , Generalized hypotonia (present) , Abnormality of coordination (present) , Cognitive impairment (present) , Short attention span (present) , Depression (present) , Anxiety (present) , Abnormal aggressive, impulsive or violent behavior (present) , Autistic behavior (present) , Joint hypermobility (present) , Abnormality of the curvature of the vertebral column (present) , Syncope (present) , Arrhythmia (present) (less)
Age: 10-19 years
Sex: female
Testing laboratory: GeneDx
Date variant was reported to submitter: 2015-07-31
Testing laboratory interpretation: Uncertain significance
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation. | Sanchez O | PloS one | 2016 | PMID: 27930701 |
First genetic analysis of aneurysm genes in familial and sporadic abdominal aortic aneurysm. | van de Luijtgaarden KM | Human genetics | 2015 | PMID: 26017485 |
New population-based exome data question the pathogenicity of some genetic variants previously associated with Marfan syndrome. | Yang RQ | BMC genetics | 2014 | PMID: 24941995 |
Actionable, pathogenic incidental findings in 1,000 participants' exomes. | Dorschner MO | American journal of human genetics | 2013 | PMID: 24055113 |
Transforming growth factor-beta receptor type II mutation in a patient with bicuspid aortic valve disease and intraoperative aortic dissection. | Girdauskas E | The Annals of thoracic surgery | 2011 | PMID: 21524434 |
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 |
A new locus-specific database (LSDB) for mutations in the TGFBR2 gene: UMD-TGFBR2. | Frederic MY | Human mutation | 2008 | PMID: 17935258 |
Patterns of somatic mutation in human cancer genomes. | Greenman C | Nature | 2007 | PMID: 17344846 |
Resequencing of genes for transforming growth factor beta1 (TGFB1) type 1 and 2 receptors (TGFBR1, TGFBR2), and association analysis of variants with diabetic nephropathy. | McKnight AJ | BMC medical genetics | 2007 | PMID: 17319955 |
Recent progress in genetics of Marfan syndrome and Marfan-associated disorders. | Mizuguchi T | Journal of human genetics | 2007 | PMID: 17061023 |
Aneurysm syndromes caused by mutations in the TGF-beta receptor. | Loeys BL | The New England journal of medicine | 2006 | PMID: 16928994 |
Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders. | Mátyás G | Human mutation | 2006 | PMID: 16791849 |
Inhibiting mutations in the transforming growth factor beta type 2 receptor in recurrent human breast cancer. | Lücke CD | Cancer research | 2001 | PMID: 11212236 |
click to load more click to collapse |
Text-mined citations for rs35766612 ...
HelpRecord last updated Apr 20, 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.