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NM_000138.5(FBN1):c.8521G>T (p.Glu2841Ter) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 5, 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:
RCV002408641.4

Allele description [Variation Report for NM_000138.5(FBN1):c.8521G>T (p.Glu2841Ter)]

NM_000138.5(FBN1):c.8521G>T (p.Glu2841Ter)

Gene:
FBN1:fibrillin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_000138.5(FBN1):c.8521G>T (p.Glu2841Ter)
HGVS:
  • NC_000015.10:g.48411085C>A
  • NG_008805.2:g.239704G>T
  • NM_000138.5:c.8521G>TMANE SELECT
  • NP_000129.3:p.Glu2841Ter
  • NP_000129.3:p.Glu2841Ter
  • LRG_778t1:c.8521G>T
  • LRG_778:g.239704G>T
  • LRG_778p1:p.Glu2841Ter
  • NC_000015.9:g.48703282C>A
  • NM_000138.4:c.8521G>T
Protein change:
E2841*
Links:
dbSNP: rs587782948
NCBI 1000 Genomes Browser:
rs587782948
Molecular consequence:
  • NM_000138.5:c.8521G>T - nonsense - [Sequence Ontology: SO:0001587]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002675459Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 5, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Evaluating Japanese patients with the Marfan syndrome using high-throughput microarray-based mutational analysis of fibrillin-1 gene.

Ogawa N, Imai Y, Takahashi Y, Nawata K, Hara K, Nishimura H, Kato M, Takeda N, Kohro T, Morita H, Taketani T, Morota T, Yamazaki T, Goto J, Tsuji S, Takamoto S, Nagai R, Hirata Y.

Am J Cardiol. 2011 Dec 15;108(12):1801-7. doi: 10.1016/j.amjcard.2011.07.053. Epub 2011 Sep 10.

PubMed [citation]
PMID:
21907952

Details of each submission

From Ambry Genetics, SCV002675459.3

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

Description

The p.E2841* pathogenic mutation (also known as c.8521G>T), located in coding exon 65 of the FBN1 gene, results from a G to T substitution at nucleotide position 8521. This changes the amino acid from a glutamic acid to a stop codon within coding exon 65. This alteration occurs at the 3' terminus of theFBN1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 31 amino acids (1%) of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This mutation has been previously reported in a cohort of patients with suspected or confirmed Marfan syndrome (Ogawa N et al. Am. J. Cardiol. 2011;108:1801-7). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Oct 20, 2024