NM_003242.6(TGFBR2):c.832A>T (p.Ile278Phe) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 27, 2021
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:: RCV000698826.5

Allele description [Variation Report for NM_003242.6(TGFBR2):c.832A>T (p.Ile278Phe)]

NM_003242.6(TGFBR2):c.832A>T (p.Ile278Phe)

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.832A>T (p.Ile278Phe)

HGVS:

NC_000003.12:g.30672015A>T
NG_007490.1:g.70514A>T
NM_001024847.3:c.907A>T
NM_001407126.1:c.1015A>T
NM_001407127.1:c.940A>T
NM_001407128.1:c.859A>T
NM_001407129.1:c.835A>T
NM_001407130.1:c.832A>T
NM_001407132.1:c.727A>T
NM_001407133.1:c.727A>T
NM_001407134.1:c.727A>T
NM_001407135.1:c.727A>T
NM_001407136.1:c.727A>T
NM_001407137.1:c.547A>T
NM_001407138.1:c.472A>T
NM_003242.6:c.832A>TMANE SELECT
NP_001020018.1:p.Ile303Phe
NP_001020018.1:p.Ile303Phe
NP_001394055.1:p.Ile339Phe
NP_001394056.1:p.Ile314Phe
NP_001394057.1:p.Ile287Phe
NP_001394058.1:p.Ile279Phe
NP_001394059.1:p.Ile278Phe
NP_001394061.1:p.Ile243Phe
NP_001394062.1:p.Ile243Phe
NP_001394063.1:p.Ile243Phe
NP_001394064.1:p.Ile243Phe
NP_001394065.1:p.Ile243Phe
NP_001394066.1:p.Ile183Phe
NP_001394067.1:p.Ile158Phe
NP_003233.4:p.Ile278Phe
LRG_779t1:c.907A>T
LRG_779t2:c.832A>T
LRG_779:g.70514A>T
LRG_779p1:p.Ile303Phe
LRG_779p2:p.Ile278Phe
NC_000003.11:g.30713507A>T
NM_001024847.2:c.907A>T
NM_003242.5:c.832A>T

Protein change:

I158F

Links:

dbSNP: rs1559466871

NCBI 1000 Genomes Browser:

rs1559466871

Molecular consequence:

NM_001024847.3:c.907A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407126.1:c.1015A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407127.1:c.940A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407128.1:c.859A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407129.1:c.835A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407130.1:c.832A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407132.1:c.727A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407133.1:c.727A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407134.1:c.727A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407135.1:c.727A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407136.1:c.727A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407137.1:c.547A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407138.1:c.472A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003242.6:c.832A>T - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000827514	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 27, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000827514

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 27, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000827514.3

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with TGFBR2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with phenylalanine at codon 278 of the TGFBR2 protein (p.Ile278Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine.

#	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: Sep 29, 2024

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