NM_003242.6(TGFBR2):c.1058C>T (p.Ser353Phe) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 13, 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:: RCV000557035.5

Allele description [Variation Report for NM_003242.6(TGFBR2):c.1058C>T (p.Ser353Phe)]

NM_003242.6(TGFBR2):c.1058C>T (p.Ser353Phe)

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.1058C>T (p.Ser353Phe)

HGVS:

NC_000003.12:g.30672241C>T
NG_007490.1:g.70740C>T
NM_001024847.3:c.1133C>T
NM_001407126.1:c.1241C>T
NM_001407127.1:c.1166C>T
NM_001407128.1:c.1085C>T
NM_001407129.1:c.1061C>T
NM_001407130.1:c.1058C>T
NM_001407132.1:c.953C>T
NM_001407133.1:c.953C>T
NM_001407134.1:c.953C>T
NM_001407135.1:c.953C>T
NM_001407136.1:c.953C>T
NM_001407137.1:c.773C>T
NM_001407138.1:c.698C>T
NM_003242.6:c.1058C>TMANE SELECT
NP_001020018.1:p.Ser378Phe
NP_001020018.1:p.Ser378Phe
NP_001394055.1:p.Ser414Phe
NP_001394056.1:p.Ser389Phe
NP_001394057.1:p.Ser362Phe
NP_001394058.1:p.Ser354Phe
NP_001394059.1:p.Ser353Phe
NP_001394061.1:p.Ser318Phe
NP_001394062.1:p.Ser318Phe
NP_001394063.1:p.Ser318Phe
NP_001394064.1:p.Ser318Phe
NP_001394065.1:p.Ser318Phe
NP_001394066.1:p.Ser258Phe
NP_001394067.1:p.Ser233Phe
NP_003233.4:p.Ser353Phe
LRG_779t1:c.1133C>T
LRG_779t2:c.1058C>T
LRG_779:g.70740C>T
LRG_779p1:p.Ser378Phe
LRG_779p2:p.Ser353Phe
NC_000003.11:g.30713733C>T
NM_001024847.2:c.1133C>T
NM_003242.5:c.1058C>T

Protein change:

S233F

Links:

dbSNP: rs1553630235

NCBI 1000 Genomes Browser:

rs1553630235

Molecular consequence:

NM_001024847.3:c.1133C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407126.1:c.1241C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407127.1:c.1166C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407128.1:c.1085C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407129.1:c.1061C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407130.1:c.1058C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407132.1:c.953C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407133.1:c.953C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407134.1:c.953C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407135.1:c.953C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407136.1:c.953C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407137.1:c.773C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407138.1:c.698C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003242.6:c.1058C>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
SCV000658811	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 13, 2023)	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

SCV000658811

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 13, 2023)

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, SCV000658811.3

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

Description

This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 353 of the TGFBR2 protein (p.Ser353Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of TGFBR2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 477533). 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%. For these reasons, this variant has been 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: Sep 29, 2024

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