NM_003242.6(TGFBR2):c.1159G>T (p.Val387Leu) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Jan 26, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000249454.25

Allele description [Variation Report for NM_003242.6(TGFBR2):c.1159G>T (p.Val387Leu)]

NM_003242.6(TGFBR2):c.1159G>T (p.Val387Leu)

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.1159G>T (p.Val387Leu)

Other names:

p.V387L:GTG>TTG

HGVS:

NC_000003.12:g.30672342G>T
NG_007490.1:g.70841G>T
NM_001024847.3:c.1234G>T
NM_001407126.1:c.1342G>T
NM_001407127.1:c.1267G>T
NM_001407128.1:c.1186G>T
NM_001407129.1:c.1162G>T
NM_001407130.1:c.1159G>T
NM_001407132.1:c.1054G>T
NM_001407133.1:c.1054G>T
NM_001407134.1:c.1054G>T
NM_001407135.1:c.1054G>T
NM_001407136.1:c.1054G>T
NM_001407137.1:c.874G>T
NM_001407138.1:c.799G>T
NM_003242.6:c.1159G>TMANE SELECT
NP_001020018.1:p.Val412Leu
NP_001020018.1:p.Val412Leu
NP_001394055.1:p.Val448Leu
NP_001394056.1:p.Val423Leu
NP_001394057.1:p.Val396Leu
NP_001394058.1:p.Val388Leu
NP_001394059.1:p.Val387Leu
NP_001394061.1:p.Val352Leu
NP_001394062.1:p.Val352Leu
NP_001394063.1:p.Val352Leu
NP_001394064.1:p.Val352Leu
NP_001394065.1:p.Val352Leu
NP_001394066.1:p.Val292Leu
NP_001394067.1:p.Val267Leu
NP_003233.4:p.Val387Leu
LRG_779t1:c.1234G>T
LRG_779t2:c.1159G>T
LRG_779:g.70841G>T
LRG_779p1:p.Val412Leu
LRG_779p2:p.Val387Leu
NC_000003.11:g.30713834G>T
NM_001024847.2:c.1234G>T
NM_003242.5:c.1159G>T

Protein change:

V267L

Links:

dbSNP: rs35766612

NCBI 1000 Genomes Browser:

rs35766612

Molecular consequence:

NM_001024847.3:c.1234G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407126.1:c.1342G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407127.1:c.1267G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407128.1:c.1186G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407129.1:c.1162G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407130.1:c.1159G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407132.1:c.1054G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407133.1:c.1054G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407134.1:c.1054G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407135.1:c.1054G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407136.1:c.1054G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407137.1:c.874G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407138.1:c.799G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003242.6:c.1159G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:: Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:: MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000319271	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Likely benign (Sep 19, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16791849, 24793577 Citation Link,
SCV000548116	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 26, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000782369	Center for Human Genetics, Inc, Center for Human Genetics, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 1, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000903193	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (May 7, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003838805	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Aug 20, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders.

Mátyás G, Arnold E, Carrel T, Baumgartner D, Boileau C, Berger W, Steinmann B.

Hum Mutat. 2006 Aug;27(8):760-9.

PubMed [citation]

PMID:: 16791849

The spectrum of FBN1, TGFβR1, TGFβR2 and ACTA2 variants in 594 individuals with suspected Marfan Syndrome, Loeys-Dietz Syndrome or Thoracic Aortic Aneurysms and Dissections (TAAD).

Lerner-Ellis JP, Aldubayan SH, Hernandez AL, Kelly MA, Stuenkel AJ, Walsh J, Joshi VA.

Mol Genet Metab. 2014 Jun;112(2):171-6. doi: 10.1016/j.ymgme.2014.03.011. Epub 2014 Apr 2.

PubMed [citation]

PMID:: 24793577

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000319271.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

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.

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

From Invitae, SCV000548116.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Human Genetics, Inc, Center for Human Genetics, Inc, SCV000782369.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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		not provided	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV000903193.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV003838805.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 20, 2024

ClinVar

Relating variation to medicine