NM_003239.5(TGFB3):c.170dup (p.Pro57_Glu58insTer) AND Rienhoff syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 15, 2022
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:: RCV002551569.9

Allele description [Variation Report for NM_003239.5(TGFB3):c.170dup (p.Pro57_Glu58insTer)]

NM_003239.5(TGFB3):c.170dup (p.Pro57_Glu58insTer)

Gene:

TGFB3:transforming growth factor beta 3 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

14q24.3

Genomic location:

Preferred name:

NM_003239.5(TGFB3):c.170dup (p.Pro57_Glu58insTer)

HGVS:

NC_000014.9:g.75980729dup
NG_011715.1:g.6026dup
NM_001329938.2:c.170dup
NM_001329939.2:c.170dup
NM_003239.5:c.170dupMANE SELECT
NP_001316867.1:p.Pro57_Glu58insTer
NP_001316868.1:p.Pro57_Glu58insTer
NP_003230.1:p.Pro57_Glu58insTer
LRG_399:g.6026dup
NC_000014.8:g.76447066_76447067insG
NC_000014.8:g.76447072dup

Links:

dbSNP: rs2140254449

NCBI 1000 Genomes Browser:

rs2140254449

Molecular consequence:

NM_001329938.2:c.170dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001329939.2:c.170dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003239.5:c.170dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Rienhoff syndrome
Synonyms:: Loeys-Dietz syndrome 5
Identifiers:: MONDO: MONDO:0014262; MedGen: C3810012; OMIM: 615582

Recent activity

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H.sapiens gene for transforming growth factor-beta 3 (TGF-beta 3) exon 1 (and jo...
H.sapiens gene for transforming growth factor-beta 3 (TGF-beta 3) exon 1 (and joined CDS)
gi|37075|emb|X14885.1|

Nucleotide
H.sapiens gene for transforming growth factor-beta 3 (TGF-beta 3) exon 5
H.sapiens gene for transforming growth factor-beta 3 (TGF-beta 3) exon 5
gi|37083|emb|X14889.1|

Nucleotide
Melanoma, Experimental
Melanoma, Experimental
Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.<br/>Year introduced: 1987

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001590476	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 15, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25835445, 26188975, 31898322, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001590476

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 15, 2022)

germline

clinical testing

PubMed (4)
[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

Mutations in a TGF-β ligand, TGFB3, cause syndromic aortic aneurysms and dissections.

Bertoli-Avella AM, Gillis E, Morisaki H, Verhagen JMA, de Graaf BM, van de Beek G, Gallo E, Kruithof BPT, Venselaar H, Myers LA, Laga S, Doyle AJ, Oswald G, van Cappellen GWA, Yamanaka I, van der Helm RM, Beverloo B, de Klein A, Pardo L, Lammens M, Evers C, Devriendt K, et al.

J Am Coll Cardiol. 2015 Apr 7;65(13):1324-1336. doi: 10.1016/j.jacc.2015.01.040.

PubMed [citation]

PMID:: 25835445
PMCID:: PMC4380321

Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting.

Ziganshin BA, Bailey AE, Coons C, Dykas D, Charilaou P, Tanriverdi LH, Liu L, Tranquilli M, Bale AE, Elefteriades JA.

Ann Thorac Surg. 2015 Nov;100(5):1604-11. doi: 10.1016/j.athoracsur.2015.04.106. Epub 2015 Jul 15.

PubMed [citation]

PMID:: 26188975

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001590476.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This sequence change creates a premature translational stop signal (p.Glu58*) in the TGFB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TGFB3 are known to be pathogenic (PMID: 25835445, 26188975). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with TGFB3-related conditions (PMID: 31898322). ClinVar contains an entry for this variant (Variation ID: 1075580). 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: Aug 25, 2024

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