NM_003242.6(TGFBR2):c.1483C>T (p.Arg495Ter) AND Loeys-Dietz syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 30, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000157519.3

Allele description [Variation Report for NM_003242.6(TGFBR2):c.1483C>T (p.Arg495Ter)]

NM_003242.6(TGFBR2):c.1483C>T (p.Arg495Ter)

Gene:

TGFBR2:transforming growth factor beta receptor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p24.1

Genomic location:

Preferred name:

NM_003242.6(TGFBR2):c.1483C>T (p.Arg495Ter)

Other names:

p.R495*:CGA>TGA

HGVS:

NC_000003.12:g.30688470C>T
NG_007490.1:g.86969C>T
NM_001024847.3:c.1558C>T
NM_001407126.1:c.1666C>T
NM_001407127.1:c.1591C>T
NM_001407128.1:c.1510C>T
NM_001407129.1:c.1486C>T
NM_001407130.1:c.1480C>T
NM_001407132.1:c.1378C>T
NM_001407133.1:c.1378C>T
NM_001407134.1:c.1378C>T
NM_001407135.1:c.1378C>T
NM_001407136.1:c.1378C>T
NM_001407137.1:c.1198C>T
NM_001407138.1:c.1123C>T
NM_001407139.1:c.613C>T
NM_003242.6:c.1483C>TMANE SELECT
NP_001020018.1:p.Arg520Ter
NP_001020018.1:p.Arg520Ter
NP_001394055.1:p.Arg556Ter
NP_001394056.1:p.Arg531Ter
NP_001394057.1:p.Arg504Ter
NP_001394058.1:p.Arg496Ter
NP_001394059.1:p.Arg494Ter
NP_001394061.1:p.Arg460Ter
NP_001394062.1:p.Arg460Ter
NP_001394063.1:p.Arg460Ter
NP_001394064.1:p.Arg460Ter
NP_001394065.1:p.Arg460Ter
NP_001394066.1:p.Arg400Ter
NP_001394067.1:p.Arg375Ter
NP_001394068.1:p.Arg205Ter
NP_003233.4:p.Arg495Ter
LRG_779t1:c.1558C>T
LRG_779t2:c.1483C>T
LRG_779:g.86969C>T
LRG_779p1:p.Arg520Ter
LRG_779p2:p.Arg495Ter
NC_000003.11:g.30729962C>T
NM_001024847.2:c.1558C>T
NM_003242.5:c.1483C>T

Protein change:

R205*; ARG495TER

Links:

OMIM: 190182.0019; dbSNP: rs104893819

Molecular consequence:

NM_001024847.3:c.1558C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407126.1:c.1666C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407127.1:c.1591C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407128.1:c.1510C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407129.1:c.1486C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407130.1:c.1480C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407132.1:c.1378C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407133.1:c.1378C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407134.1:c.1378C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407135.1:c.1378C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407136.1:c.1378C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407137.1:c.1198C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407138.1:c.1123C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407139.1:c.613C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_003242.6:c.1483C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Loeys-Dietz syndrome (LDS)
Identifiers:: MONDO: MONDO:0018954; MedGen: C2697932; OMIM: PS609192

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000207264	Blueprint Genetics	no assertion criteria provided	Likely pathogenic (Jul 21, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000918308	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jan 30, 2018)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16928994, 17935258, 27879313, 21267002, 18084123, 22113417 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000207264

Blueprint Genetics

no assertion criteria provided

Likely pathogenic
(Jul 21, 2014)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000918308

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jan 30, 2018)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Aneurysm syndromes caused by mutations in the TGF-beta receptor.

Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, De Backer JF, Oswald GL, Symoens S, Manouvrier S, Roberts AE, Faravelli F, Greco MA, Pyeritz RE, Milewicz DM, Coucke PJ, Cameron DE, Braverman AC, Byers PH, De Paepe AM, Dietz HC.

N Engl J Med. 2006 Aug 24;355(8):788-98.

PubMed [citation]

PMID:: 16928994

A new locus-specific database (LSDB) for mutations in the TGFBR2 gene: UMD-TGFBR2.

Frederic MY, Hamroun D, Faivre L, Boileau C, Jondeau G, Claustres M, Béroud C, Collod-Béroud G.

Hum Mutat. 2008 Jan;29(1):33-8.

PubMed [citation]

PMID:: 17935258

See all PubMed Citations (6)

Details of each submission

From Blueprint Genetics, SCV000207264.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000918308.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Variant summary: TGFBR2 c.1483C>T (p.Arg495X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 245910 control chromosomes. The c.1483C>T variant has been reported in the literature in multiple individuals affected with Loeys-Dietz Syndrome, including segregation with disease in a family (Togashi_2007). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, where an increase in intracellular collagen was observed in patient fibroblasts (Barnett_2011). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, each of which classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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