NM_000138.5(FBN1):c.4577G>A (p.Cys1526Tyr) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 28, 2015
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:: RCV002311132.9

Allele description [Variation Report for NM_000138.5(FBN1):c.4577G>A (p.Cys1526Tyr)]

NM_000138.5(FBN1):c.4577G>A (p.Cys1526Tyr)

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.4577G>A (p.Cys1526Tyr)

HGVS:

NC_000015.10:g.48468417C>T
NG_008805.2:g.182372G>A
NM_000138.5:c.4577G>AMANE SELECT
NP_000129.3:p.Cys1526Tyr
NP_000129.3:p.Cys1526Tyr
LRG_778t1:c.4577G>A
LRG_778:g.182372G>A
LRG_778p1:p.Cys1526Tyr
NC_000015.9:g.48760614C>T
NM_000138.4:c.4577G>A

Protein change:

C1526Y

Links:

dbSNP: rs886039120

NCBI 1000 Genomes Browser:

rs886039120

Molecular consequence:

NM_000138.5:c.4577G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

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Chromosome neighbors for GEO Profiles (Select 90840384) (20)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 90844088) (20)
GEO Profiles
IGFBP7 insulin like growth factor binding protein 7 [Homo sapiens]
IGFBP7 insulin like growth factor binding protein 7 [Homo sapiens]
Gene ID:3490

Gene
Gene Links for GEO Profiles (Select 90837011) (1)
Gene
rap1 GTPase-activating protein 2 isoform X3 [Homo sapiens]
rap1 GTPase-activating protein 2 isoform X3 [Homo sapiens]
gi|2217310836|ref|XP_047291624.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000320168	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Aug 28, 2015)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18087243, 19839986 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000320168

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Aug 28, 2015)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Is ectopia lentis in some cases a mild phenotypic expression of Marfan syndrome? Need for a long-term follow-up.

Pepe G, Lapini I, Evangelisti L, Attanasio M, Giusti B, Lucarini L, Fattori R, Pellicanò G, Scrivanti M, Porciani MC, Abbate R, Gensini GF.

Mol Vis. 2007 Nov 29;13:2242-7.

PubMed [citation]

PMID:: 18087243

Mutation spectrum of the fibrillin-1 (FBN1) gene in Taiwanese patients with Marfan syndrome.

Hung CC, Lin SY, Lee CN, Cheng HY, Lin SP, Chen MR, Chen CP, Chang CH, Lin CY, Yu CC, Chiu HH, Cheng WF, Ho HN, Niu DM, Su YN.

Ann Hum Genet. 2009 Nov;73(Pt 6):559-67. doi: 10.1111/j.1469-1809.2009.00545.x.

PubMed [citation]

PMID:: 19839986

Details of each submission

From Ambry Genetics, SCV000320168.7

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

Description

The p.C1526Y variant (also known as c.4577G>A), located in coding exon 36 of the FBN1 gene, results from a G to A substitution at nucleotide position 4577. The cysteine at codon 1526 is replaced by tyrosine, an amino acid with highly dissimilar properties, and is located in the cb EGF-like #22 domain. This alteration was first reported in a patient from Taiwan who met Ghent criteria for Marfan syndrome (MFS); symptoms included cardiovascular and ocular features of MFS (Hung CC et al. Ann Hum Genet. 2009;73(Pt 6):559-67). In addition, another alteration at this codon, p.C1526S, has been reported in an individual with ectopia lentis (Pepe G et al. Mol Vis. 2007;13:2242-7). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6494 samples (12988 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of evidence available, this variant is likely to be 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: Sep 8, 2024

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