NM_003242.6(TGFBR2):c.1202C>T (p.Ser401Phe) 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:: Jul 26, 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:: RCV000810644.4

Allele description

NM_003242.6(TGFBR2):c.1202C>T (p.Ser401Phe)

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.1202C>T (p.Ser401Phe)

HGVS:

NC_000003.12:g.30672385C>T
NG_007490.1:g.70884C>T
NM_001024847.3:c.1277C>T
NM_001407126.1:c.1385C>T
NM_001407127.1:c.1310C>T
NM_001407128.1:c.1229C>T
NM_001407129.1:c.1205C>T
NM_001407130.1:c.1202C>T
NM_001407132.1:c.1097C>T
NM_001407133.1:c.1097C>T
NM_001407134.1:c.1097C>T
NM_001407135.1:c.1097C>T
NM_001407136.1:c.1097C>T
NM_001407137.1:c.917C>T
NM_001407138.1:c.842C>T
NM_003242.6:c.1202C>TMANE SELECT
NP_001020018.1:p.Ser426Phe
NP_001020018.1:p.Ser426Phe
NP_001394055.1:p.Ser462Phe
NP_001394056.1:p.Ser437Phe
NP_001394057.1:p.Ser410Phe
NP_001394058.1:p.Ser402Phe
NP_001394059.1:p.Ser401Phe
NP_001394061.1:p.Ser366Phe
NP_001394062.1:p.Ser366Phe
NP_001394063.1:p.Ser366Phe
NP_001394064.1:p.Ser366Phe
NP_001394065.1:p.Ser366Phe
NP_001394066.1:p.Ser306Phe
NP_001394067.1:p.Ser281Phe
NP_003233.4:p.Ser401Phe
LRG_779t1:c.1277C>T
LRG_779t2:c.1202C>T
LRG_779:g.70884C>T
LRG_779p1:p.Ser426Phe
LRG_779p2:p.Ser401Phe
NC_000003.11:g.30713877C>T
NM_001024847.2:c.1277C>T
NM_003242.5:c.1202C>T

Protein change:

S281F

Links:

dbSNP: rs1575158141

NCBI 1000 Genomes Browser:

rs1575158141

Molecular consequence:

NM_001024847.3:c.1277C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407126.1:c.1385C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407127.1:c.1310C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407128.1:c.1229C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407129.1:c.1205C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407130.1:c.1202C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407132.1:c.1097C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407133.1:c.1097C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407134.1:c.1097C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407135.1:c.1097C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407136.1:c.1097C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407137.1:c.917C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407138.1:c.842C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003242.6:c.1202C>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

Recent activity

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Homo sapiens mRNA; cDNA DKFZp451M129 (from clone DKFZp451M129)
Homo sapiens mRNA; cDNA DKFZp451M129 (from clone DKFZp451M129)
gi|21733936|emb|AL833302.1|

Nucleotide
putative membrane protein (plasmid) [Peptoclostridium acidaminophilum DSM 3953]
putative membrane protein (plasmid) [Peptoclostridium acidaminophilum DSM 3953]
gi|595614154|gnl|goetting|EAL2_808p |gb|AHM57798.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000950866	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 26, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27879313, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000950866

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 26, 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

International Registry of Patients Carrying TGFBR1 or TGFBR2 Mutations: Results of the MAC (Montalcino Aortic Consortium).

Jondeau G, Ropers J, Regalado E, Braverman A, Evangelista A, Teixedo G, De Backer J, Muiño-Mosquera L, Naudion S, Zordan C, Morisaki T, Morisaki H, Von Kodolitsch Y, Dupuis-Girod S, Morris SA, Jeremy R, Odent S, Adès LC, Bakshi M, Holman K, LeMaire S, Milleron O, et al.

Circ Cardiovasc Genet. 2016 Dec;9(6):548-558. doi: 10.1161/CIRCGENETICS.116.001485. Epub 2016 Nov 21.

PubMed [citation]

PMID:: 27879313
PMCID:: PMC5177493

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, SCV000950866.3

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

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. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt TGFBR2 function. ClinVar contains an entry for this variant (Variation ID: 654639). This missense change has been observed in individual(s) with clinical features of TGFBR2-related conditions (PMID: 27879313; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 401 of the TGFBR2 protein (p.Ser401Phe).

#	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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