NM_000138.5(FBN1):c.3623G>T (p.Cys1208Phe) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 22, 2016
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:: RCV002314341.9

Allele description [Variation Report for NM_000138.5(FBN1):c.3623G>T (p.Cys1208Phe)]

NM_000138.5(FBN1):c.3623G>T (p.Cys1208Phe)

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.3623G>T (p.Cys1208Phe)

HGVS:

NC_000015.10:g.48485463C>A
NG_008805.2:g.165326G>T
NM_000138.5:c.3623G>TMANE SELECT
NP_000129.3:p.Cys1208Phe
NP_000129.3:p.Cys1208Phe
LRG_778t1:c.3623G>T
LRG_778:g.165326G>T
LRG_778p1:p.Cys1208Phe
NC_000015.9:g.48777660C>A
NM_000138.4:c.3623G>T

Protein change:

C1208F

Links:

dbSNP: rs1555398406

NCBI 1000 Genomes Browser:

rs1555398406

Molecular consequence:

NM_000138.5:c.3623G>T - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000738855	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 22, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11175294, 16571647, 19117906, 8136837 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000738855

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 22, 2016)

germline

clinical testing

PubMed (4)
[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

Classic, atypically severe and neonatal Marfan syndrome: twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40.

Tiecke F, Katzke S, Booms P, Robinson PN, Neumann L, Godfrey M, Mathews KR, Scheuner M, Hinkel GK, Brenner RE, Hövels-Gürich HH, Hagemeier C, Fuchs J, Skovby F, Rosenberg T.

Eur J Hum Genet. 2001 Jan;9(1):13-21.

PubMed [citation]

PMID:: 11175294

The molecular genetics of Marfan syndrome and related disorders.

Robinson PN, Arteaga-Solis E, Baldock C, Collod-Béroud G, Booms P, De Paepe A, Dietz HC, Guo G, Handford PA, Judge DP, Kielty CM, Loeys B, Milewicz DM, Ney A, Ramirez F, Reinhardt DP, Tiedemann K, Whiteman P, Godfrey M.

J Med Genet. 2006 Oct;43(10):769-87. Epub 2006 Mar 29. Review.

PubMed [citation]

PMID:: 16571647
PMCID:: PMC2563177

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000738855.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.C1208F pathogenic mutation (also known as c.3623G>T), located in coding exon 29 of the FBN1 gene, results from a G to T substitution at nucleotide position 3623. The cysteine at codon 1208 is replaced by phenylalanine, an amino acid with highly dissimilar properties, and is located in a cb EGF-like domain. This alteration has been determined to be the result of a de novo mutation or germline mosaicism in one family with an isolated case of early onset Marfan syndrome (MFS). Mutations in exons 24-32 of the FBN1 gene have been reported at higher proportions in cases of neonatal MFS and in children with suspected MFS compared to adults with the condition (Robinson PN et al. J. Med. Genet., 2006 Oct;43:769-87; Tiecke F et al. Eur. J. Hum. Genet., 2001 Jan;9:13-21; Faivre L et al. Pediatrics, 2009 Jan;123:391-8). The majority of FBN1 mutations identified to date have involved the substitution or generation of cysteine residues within cbEGF domains (Vollbrandt T et al. J Biol Chem. 2004;279(31):32924-32931). Based on the supporting evidence, 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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