NM_003238.6(TGFB2):c.958C>T (p.Arg320Cys) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 25, 2024
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:: RCV004678752.1

Allele description [Variation Report for NM_003238.6(TGFB2):c.958C>T (p.Arg320Cys)]

NM_003238.6(TGFB2):c.958C>T (p.Arg320Cys)

Gene:

TGFB2:transforming growth factor beta 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_003238.6(TGFB2):c.958C>T (p.Arg320Cys)

HGVS:

NC_000001.11:g.218437368C>T
NG_027721.2:g.97035C>T
NM_001135599.4:c.1042C>T
NM_003238.6:c.958C>TMANE SELECT
NP_001129071.1:p.Arg348Cys
NP_003229.1:p.Arg320Cys
NC_000001.10:g.218610710C>T
NM_001135599.2:c.1042C>T
NM_003238.3:c.958C>T
NM_003238.4:c.958C>T
NR_138148.2:n.2209C>T
NR_138149.2:n.2293C>T

Protein change:

R320C; ARG348CYS

Links:

OMIM: 190220.0005; dbSNP: rs1553303352

NCBI 1000 Genomes Browser:

rs1553303352

Molecular consequence:

NM_001135599.4:c.1042C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003238.6:c.958C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_138148.2:n.2209C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_138149.2:n.2293C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Glycine Plasma Membrane Transport Proteins
Glycine Plasma Membrane Transport Proteins
A family of sodium chloride-dependent neurotransmitter symporters that transport the amino acid GLYCINE. They differ from GLYCINE RECEPTORS, which signal cellular responses to...<br/>Year introduced: 2006(1987)

MeSH
Vochysia rufa (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005170142	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Apr 25, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25046559, 27782106 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005170142

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Apr 25, 2024)

germline

clinical testing

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

Citation Link

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

Whole exome sequencing for the identification of a new mutation in TGFB2 involved in a familial case of non-syndromic aortic disease.

Gago-Díaz M, Blanco-Verea A, Teixidó-Turà G, Valenzuela I, Del Campo M, Borregan M, Sobrino B, Amigo J, García-Dorado D, Evangelista A, Carracedo A, Brion M.

Clin Chim Acta. 2014 Nov 1;437:88-92. doi: 10.1016/j.cca.2014.07.016. Epub 2014 Jul 19.

PubMed [citation]

PMID:: 25046559

A missense TGFB2 variant p.(Arg320Cys) causes a paradoxical and striking increase in aortic TGFB1/2 expression.

Al Maskari R, Yasmin, Cleary S, Figg N, Mehta S, Rassl D, Wilkinson I, O'Shaughnessy KM.

Eur J Hum Genet. 2016 Jan;25(1):157-160. doi: 10.1038/ejhg.2016.143. Epub 2016 Oct 26.

PubMed [citation]

PMID:: 27782106
PMCID:: PMC5149071

Details of each submission

From Ambry Genetics, SCV005170142.1

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

Description

The p.R320C variant (also known as c.958C>T), located in coding exon 6 of the TGFB2 gene, results from a C to T substitution at nucleotide position 958. The arginine at codon 320 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant (also referred to as NM_001135599.2:c.1042C>T, p.R348C) was reported in unrelated individuals with thoracic aortic aneurysm and dissection with and without mild systemic connective tissue disease features, and segregated with disease in families (Gago-Díaz M et al. Clin. Chim. Acta, 2014 Nov;437:88-92; Al Maskari R et al. Eur. J. Hum. Genet., 2016 01;25:157-160). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be 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: Nov 3, 2024

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