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NM_004612.4(TGFBR1):c.926C>T (p.Thr309Met) AND Loeys-Dietz syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 18, 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:
RCV004010679.2

Allele description [Variation Report for NM_004612.4(TGFBR1):c.926C>T (p.Thr309Met)]

NM_004612.4(TGFBR1):c.926C>T (p.Thr309Met)

Gene:
TGFBR1:transforming growth factor beta receptor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q22.33
Genomic location:
Preferred name:
NM_004612.4(TGFBR1):c.926C>T (p.Thr309Met)
HGVS:
  • NC_000009.12:g.99142656C>T
  • NG_007461.1:g.42527C>T
  • NM_001130916.3:c.695C>T
  • NM_001306210.2:c.938C>T
  • NM_004612.4:c.926C>TMANE SELECT
  • NP_001124388.1:p.Thr232Met
  • NP_001293139.1:p.Thr313Met
  • NP_004603.1:p.Thr309Met
  • NC_000009.11:g.101904938C>T
  • NM_004612.2:c.926C>T
Protein change:
T232M
Links:
dbSNP: rs200518416
NCBI 1000 Genomes Browser:
rs200518416
Molecular consequence:
  • NM_001130916.3:c.695C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001306210.2:c.938C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004612.4:c.926C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
6

Condition(s)

Name:
Loeys-Dietz syndrome (LDS)
Identifiers:
MONDO: MONDO:0018954; MedGen: C2697932; OMIM: PS609192

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004819684All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 18, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown6not providednot provided108544not providedclinical testing

Citations

PubMed

Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: SMAD6 as an Important Contributor.

Gillis E, Kumar AA, Luyckx I, Preuss C, Cannaerts E, van de Beek G, Wieschendorf B, Alaerts M, Bolar N, Vandeweyer G, Meester J, Wünnemann F, Gould RA, Zhurayev R, Zerbino D, Mohamed SA, Mital S, Mertens L, Björck HM, Franco-Cereceda A, McCallion AS, Van Laer L, et al.

Front Physiol. 2017;8:400. doi: 10.3389/fphys.2017.00400. Erratum in: Front Physiol. 2017 Sep 25;8:730. doi: 10.3389/fphys.2017.00730.

PubMed [citation]
PMID:
28659821
PMCID:
PMC5469151

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004819684.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided6not providednot providedclinical testing PubMed (2)

Description

This missense variant replaces threonine with methionine at codon 309 of the TGFBR1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with bicuspid aortic valve and thoracic aortic aneurysm (PMID: 28659821). This variant has been identified in 8/282486 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided6not providednot providednot provided

Last Updated: Sep 29, 2024