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NM_000138.5(FBN1):c.4539C>G (p.Cys1513Trp) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 20, 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:
RCV000550970.8

Allele description [Variation Report for NM_000138.5(FBN1):c.4539C>G (p.Cys1513Trp)]

NM_000138.5(FBN1):c.4539C>G (p.Cys1513Trp)

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.4539C>G (p.Cys1513Trp)
HGVS:
  • NC_000015.10:g.48468455G>C
  • NG_008805.2:g.182334C>G
  • NM_000138.5:c.4539C>GMANE SELECT
  • NP_000129.3:p.Cys1513Trp
  • NP_000129.3:p.Cys1513Trp
  • LRG_778t1:c.4539C>G
  • LRG_778:g.182334C>G
  • LRG_778p1:p.Cys1513Trp
  • NC_000015.9:g.48760652G>C
  • NM_000138.4:c.4539C>G
Protein change:
C1513W
Links:
dbSNP: rs1555397203
NCBI 1000 Genomes Browser:
rs1555397203
Molecular consequence:
  • NM_000138.5:c.4539C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Marfan syndrome (MFS)
Synonyms:
MARFAN SYNDROME, TYPE I; Marfan syndrome type 1; Marfan's syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007947; MedGen: C0024796; Orphanet: 284963; Orphanet: 558; OMIM: 154700
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
SCV000627919Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 20, 2017) 		germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Epidermal growth factor. Location of disulfide bonds.

Savage CR Jr, Hash JH, Cohen S.

J Biol Chem. 1973 Nov 25;248(22):7669-72. No abstract available.

PubMed [citation]
PMID:
4750422

Fibrillin-1 misfolding and disease.

Whiteman P, Hutchinson S, Handford PA.

Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):338-46. Review.

PubMed [citation]
PMID:
16677079
See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000627919.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This variant generates a cysteine residue in an epidermal-growth-factor (EGF)–like domain of the FBN1 protein. Cysteine residues in these domains have been shown to be involved in the formation of disulfide bridges, which are critical for FBN1 protein structure and stability (PMID: 4750422, 16677079). Cysteine creating variants in these domains have been shown to affect protein stability and are overrepresented among individuals with Marfan syndrome (PMID: 15161917, 16571647, 17701892). For these reasons, this variant has been classified as Pathogenic. This variant has been reported in individuals affected with Marfan syndrome (PMID: 16476890, 17627385, 19293843). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tryptophan at codon 1513 of the FBN1 protein (p.Cys1513Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan.

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

Last Updated: Sep 29, 2024