NM_000138.5(FBN1):c.8547T>A (p.Tyr2849Ter) AND Familial thoracic aortic aneurysm and aortic dissection

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 13, 2017
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:: RCV002447822.1

Allele description

NM_000138.5(FBN1):c.8547T>A (p.Tyr2849Ter)

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.8547T>A (p.Tyr2849Ter)

HGVS:

NC_000015.10:g.48411059A>T
NG_008805.2:g.239730T>A
NM_000138.5:c.8547T>AMANE SELECT
NM_001406716.1:c.8547T>A
NP_000129.3:p.Tyr2849Ter
NP_000129.3:p.Tyr2849Ter
NP_001393645.1:p.Tyr2849Ter
LRG_778t1:c.8547T>A
LRG_778:g.239730T>A
LRG_778p1:p.Tyr2849Ter
NC_000015.9:g.48703256A>T
NM_000138.4:c.8547T>A

Protein change:

Y2849*

Molecular consequence:

NM_000138.5:c.8547T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406716.1:c.8547T>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002678905	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Pathogenic (Jan 13, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21034599, 27611364 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002678905

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Pathogenic
(Jan 13, 2017)

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	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Identification of a novel lethal fibrillin-1 gene mutation in a Chinese Marfan family and correlation of 3' fibrillin-1 gene mutations with phenotype.

Gao LG, Zhang L, Song L, Wang H, Chang Q, Wu YB, Hui RT, Zhou XL.

Chin Med J (Engl). 2010 Oct;123(20):2874-8.

PubMed [citation]

PMID:: 21034599

Genetic testing of 248 Chinese aortopathy patients using a panel assay.

Yang H, Luo M, Fu Y, Cao Y, Yin K, Li W, Meng C, Ma Y, Zhang J, Fan Y, Shu C, Chang Q, Zhou Z.

Sci Rep. 2016 Sep 9;6:33002. doi: 10.1038/srep33002.

PubMed [citation]

PMID:: 27611364
PMCID:: PMC5017237

Details of each submission

From Ambry Genetics, SCV002678905.1

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

Description

The p.Y2849* pathogenic mutation (also known as c.8547T>A), located in coding exon 65 of the FBN1 gene, results from a T to A substitution at nucleotide position 8547. This changes the amino acid from a tyrosine to a stop codon within coding exon 65. This alteration was described in a family with Marfan syndrome, and was absent in one unaffected family member and healthy controls (Gao LG et al. Chin. Med. J., 2010 Oct;123:2874-8). This alteration was also reported in a cohort of patients with aortopathy and suspected Marfan syndrome; however, no clinical details were provided about the mutation carrier (Yang H et al. Sci Rep, 2016 Sep;6:33002). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Nov 29, 2022

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