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NM_003239.5(TGFB3):c.886_893dup (p.Lys298fs) AND Rienhoff syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 21, 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:
RCV003583166.2

Allele description [Variation Report for NM_003239.5(TGFB3):c.886_893dup (p.Lys298fs)]

NM_003239.5(TGFB3):c.886_893dup (p.Lys298fs)

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.886_893dup (p.Lys298fs)
HGVS:
  • NC_000014.9:g.75963349_75963356dup
  • NG_011715.1:g.23394_23401dup
  • NM_001329938.2:c.886_893dup
  • NM_001329939.2:c.886_893dup
  • NM_003239.5:c.886_893dupMANE SELECT
  • NP_001316867.1:p.Lys298fs
  • NP_001316868.1:p.Lys298fs
  • NP_003230.1:p.Lys298fs
  • LRG_399:g.23394_23401dup
  • NC_000014.8:g.76429691_76429692insTTCCTCTG
  • NC_000014.8:g.76429692_76429699dup
  • NM_003239.2:c.886_893dupCAGAGGAA
Protein change:
K298fs
Links:
dbSNP: rs1555360368
NCBI 1000 Genomes Browser:
rs1555360368
Molecular consequence:
  • NM_001329938.2:c.886_893dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001329939.2:c.886_893dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_003239.5:c.886_893dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004369394Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jul 21, 2023)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Phenotypic spectrum of TGFB3 disease-causing variants in a Dutch-French cohort and first report of a homozygous patient.

Marsili L, Overwater E, Hanna N, Baujat G, Baars MJH, Boileau C, Bonneau D, Brehin AC, Capri Y, Cheung HY, Dulfer E, Gerard M, Gouya L, Hilhorst-Hofstee Y, Houweling AC, Isidor B, Le Gloan L, Menke LA, Odent S, Morice-Picard F, Vanlerberghe C, Voorhoeve E, et al.

Clin Genet. 2020 May;97(5):723-730. doi: 10.1111/cge.13700. Epub 2020 Jan 16.

PubMed [citation]
PMID:
31898322
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004369394.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Lys298Asnfs*74) in the TGFB3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 115 amino acid(s) of the TGFB3 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TGFB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 450223). This variant disrupts a region of the TGFB3 protein in which other variant(s) (p.Arg300Trp) have been determined to be pathogenic (PMID: 25835445, 31898322). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024