NM_003242.6(TGFBR2):c.1191C>G (p.Asp397Glu) AND Familial thoracic aortic aneurysm and aortic dissection

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 15, 2023
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:: RCV003528542.1

Allele description

NM_003242.6(TGFBR2):c.1191C>G (p.Asp397Glu)

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.1191C>G (p.Asp397Glu)

HGVS:

NC_000003.12:g.30672374C>G
NG_007490.1:g.70873C>G
NM_001024847.3:c.1266C>G
NM_001407126.1:c.1374C>G
NM_001407127.1:c.1299C>G
NM_001407128.1:c.1218C>G
NM_001407129.1:c.1194C>G
NM_001407130.1:c.1191C>G
NM_001407132.1:c.1086C>G
NM_001407133.1:c.1086C>G
NM_001407134.1:c.1086C>G
NM_001407135.1:c.1086C>G
NM_001407136.1:c.1086C>G
NM_001407137.1:c.906C>G
NM_001407138.1:c.831C>G
NM_001407139.1:c.530-16013C>G
NM_003242.6:c.1191C>GMANE SELECT
NP_001020018.1:p.Asp422Glu
NP_001020018.1:p.Asp422Glu
NP_001394055.1:p.Asp458Glu
NP_001394056.1:p.Asp433Glu
NP_001394057.1:p.Asp406Glu
NP_001394058.1:p.Asp398Glu
NP_001394059.1:p.Asp397Glu
NP_001394061.1:p.Asp362Glu
NP_001394062.1:p.Asp362Glu
NP_001394063.1:p.Asp362Glu
NP_001394064.1:p.Asp362Glu
NP_001394065.1:p.Asp362Glu
NP_001394066.1:p.Asp302Glu
NP_001394067.1:p.Asp277Glu
NP_003233.4:p.Asp397Glu
LRG_779t1:c.1266C>G
LRG_779t2:c.1191C>G
LRG_779:g.70873C>G
LRG_779p1:p.Asp422Glu
LRG_779p2:p.Asp397Glu
NC_000003.11:g.30713866C>G
NM_001024847.2:c.1266C>G

Protein change:

D277E

Molecular consequence:

NM_001407139.1:c.530-16013C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001024847.3:c.1266C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407126.1:c.1374C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407127.1:c.1299C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407128.1:c.1218C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407129.1:c.1194C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407130.1:c.1191C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407132.1:c.1086C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407133.1:c.1086C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407134.1:c.1086C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407135.1:c.1086C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407136.1:c.1086C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407137.1:c.906C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407138.1:c.831C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003242.6:c.1191C>G - 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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laminin subunit alpha-2 isoform X6 [Rattus norvegicus]
laminin subunit alpha-2 isoform X6 [Rattus norvegicus]
gi|2678867531|ref|XP_063120707.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004248685	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18781618, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004248685

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 15, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

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, Collod-Béroud G, Faivre L, Gouya L, Sultan G, Le Parc JM, Moura B, Attias D, Muti C, Sznajder M, Claustres M, Junien C, Baumann C, Cormier-Daire V, Rio M, Lyonnet S, Plauchu H, Lacombe D, Chevallier B, Jondeau G, Boileau C.

Hum Mutat. 2008 Nov;29(11):E284-95. doi: 10.1002/humu.20871.

PubMed [citation]

PMID:: 18781618

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 Invitae, SCV004248685.1

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

Description

This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 397 of the TGFBR2 protein (p.Asp397Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with TGFBR2-related conditions (PMID: 18781618; Invitae). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TGFBR2 protein function with a positive predictive value of 95%. 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.

#	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: Feb 20, 2024

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