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NM_000138.5(FBN1):c.2723G>A (p.Cys908Tyr) AND Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 5, 2018
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:
RCV000780256.8

Allele description [Variation Report for NM_000138.5(FBN1):c.2723G>A (p.Cys908Tyr)]

NM_000138.5(FBN1):c.2723G>A (p.Cys908Tyr)

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.2723G>A (p.Cys908Tyr)
HGVS:
  • NC_000015.10:g.48494209C>T
  • NG_008805.2:g.156580G>A
  • NM_000138.5:c.2723G>AMANE SELECT
  • NP_000129.3:p.Cys908Tyr
  • NP_000129.3:p.Cys908Tyr
  • LRG_778t1:c.2723G>A
  • LRG_778:g.156580G>A
  • LRG_778p1:p.Cys908Tyr
  • NC_000015.9:g.48786406C>T
  • NM_000138.4:c.2723G>A
Protein change:
C908Y
Links:
dbSNP: rs1057523406
NCBI 1000 Genomes Browser:
rs1057523406
Molecular consequence:
  • NM_000138.5:c.2723G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections
Identifiers:
MedGen: CN229799

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000917366Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Sep 5, 2018) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Characterization of microsatellite markers flanking FBN1: utility in the diagnostic evaluation for Marfan syndrome.

Judge DP, Biery NJ, Dietz HC.

Am J Med Genet. 2001 Feb 15;99(1):39-47.

PubMed [citation]
PMID:
11170092

The roles of two novel FBN1 gene mutations in the genotype-phenotype correlations of Marfan syndrome and ectopia lentis patients with marfanoid habitus.

Li D, Yu J, Gu F, Pang X, Ma X, Li R, Liu N, Ma X.

Genet Test. 2008 Jun;12(2):325-30. doi: 10.1089/gte.2008.0002.

PubMed [citation]
PMID:
18471089

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917366.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: FBN1 c.2723G>A (p.Cys908Tyr) results in a non-conservative amino acid change located to the second hybrid motif (Li 2008) in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246192 control chromosomes (gnomAD and publication data). The variant, c.2723G>A, has been reported in the literature in multiple individuals affected with Marfan Syndrome (Judge 2001, Li 2008). The variant was shown to segregate with the disease in these two families, with all the patients having somewhat atypical (i.e. mild to moderate) features. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Oct 26, 2024