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NM_000138.5(FBN1):c.4710G>T (p.Trp1570Cys) AND Stiff skin syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 12, 2001
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000017933.37

Allele description [Variation Report for NM_000138.5(FBN1):c.4710G>T (p.Trp1570Cys)]

NM_000138.5(FBN1):c.4710G>T (p.Trp1570Cys)

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.4710G>T (p.Trp1570Cys)
Other names:
FBN1, TRP1570CYS, 4710G-T; W1570C
HGVS:
  • NC_000015.10:g.48467975C>A
  • NG_008805.2:g.182814G>T
  • NM_000138.5:c.4710G>TMANE SELECT
  • NP_000129.3:p.Trp1570Cys
  • NP_000129.3:p.Trp1570Cys
  • LRG_778t1:c.4710G>T
  • LRG_778:g.182814G>T
  • LRG_778p1:p.Trp1570Cys
  • NC_000015.9:g.48760172C>A
  • NM_000138.4:c.4710G>T
Protein change:
TRP1570CYS
Links:
OMIM: 134797.0050; dbSNP: rs267606799
NCBI 1000 Genomes Browser:
rs267606799
Molecular consequence:
  • NM_000138.5:c.4710G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Stiff skin syndrome (SSKS)
Identifiers:
MONDO: MONDO:0008492; MedGen: C1861456; OMIM: 184900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000038212OMIM
no assertion criteria provided
Pathogenic
(Nov 12, 2001) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome.

Loeys B, Nuytinck L, Delvaux I, De Bie S, De Paepe A.

Arch Intern Med. 2001 Nov 12;161(20):2447-54.

PubMed [citation]
PMID:
11700157

A microfibril assembly assay identifies different mechanisms of dominance underlying Marfan syndrome, stiff skin syndrome and acromelic dysplasias.

Jensen SA, Iqbal S, Bulsiewicz A, Handford PA.

Hum Mol Genet. 2015 Aug 1;24(15):4454-63. doi: 10.1093/hmg/ddv181. Epub 2015 May 15.

PubMed [citation]
PMID:
25979247
PMCID:
PMC4492404

Details of each submission

From OMIM, SCV000038212.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In affected members of a 5-generation family segregating autosomal dominant stiff skin syndrome (184900), Loeys et al. (2010) identified heterozygosity for a 4710G-T transversion in exon 37 of the FBN1 gene, resulting in a trp1570-to-cys (W1570C) substitution at a key structural residue in the N-terminal portion of the fourth TGF-beta (190180)-binding protein-like domain (N-TB4). The mutation was not found in more than 400 ethnically matched control chromosomes.

In transiently transfected HEK293 cells and in the MSU-1.1 human fibroblast cell line, Jensen et al. (2015) demonstrated that the W1570C mutant is secreted into the extracellular media and incorporates into the microfibril network.

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

Last Updated: Nov 10, 2024