Skip to main page content
Accesskeys

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000138.4(FBN1):c.6806T>C (p.Ile2269Thr)

Help
Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(2);Pathogenic(6);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
9 (Most recent: Jan 29, 2019)
Last evaluated:
Jul 12, 2018
Accession:
VCV000036107.2
Variation ID:
36107
Description:
single nucleotide variant
Help

NM_000138.4(FBN1):c.6806T>C (p.Ile2269Thr)

Allele ID
44771
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q21.1
Genomic location
15: 48430736 (GRCh38) GRCh38 UCSC
15: 48722933 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.9:g.48722933A>G
NC_000015.10:g.48430736A>G
LRG_778t1:c.6806T>C LRG_778p1:p.Ile2269Thr
... more HGVS
Protein change
I2269T
Other names
-
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
dbSNP: rs193922228
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, multiple submitters, no conflicts Nov 1, 2016 RCV000029769.6
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Jul 12, 2018 RCV000255307.3
Likely pathogenic 1 criteria provided, single submitter Sep 17, 2015 RCV000246714.1
Pathogenic 1 criteria provided, single submitter May 18, 2017 RCV000515227.1
Pathogenic 1 criteria provided, single submitter Mar 28, 2018 RCV000534047.3
Pathogenic 1 criteria provided, single submitter Mar 1, 2017 RCV000586646.2
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
FBN1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
2810 2867

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(May 18, 2017)
criteria provided, single submitter
Method: clinical testing
Acromicric dysplasia
Ectopia lentis, isolated, autosomal dominant
Marfan syndrome
Stiff skin syndrome
MASS syndrome
Weill-Marchesani syndrome 2
Geleophysic dysplasia 2
Marfan lipodystrophy syndrome
Allele origin: unknown
Fulgent Genetics
Accession: SCV000611193.1
Submitted: (May 23, 2017)
Evidence details
Pathogenic
(Jan 26, 2016)
criteria provided, single submitter
Method: clinical testing
Marfan syndrome
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine
Accession: SCV000058900.5
Submitted: (Feb 23, 2018)
Evidence details
Publications
PubMed (8)
Comment:
The p.Ile2269Thr variant in FBN1 has been reported in 9 individuals with Marfan syndrome or features of Marfan syndrome, including 2 individuals in whom the ... (more)
Pathogenic
(Mar 01, 2017)
criteria provided, single submitter
Method: clinical testing
Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections
Allele origin: germline
Integrated Genetics/Laboratory Corporation of America
Accession: SCV000695589.2
Submitted: (Apr 11, 2018)
Evidence details
Publications
PubMed (11)
Comment:
Variant summary: The FBN1 c.6806T>C (p.Ile2269Thr) variant involves the missense alteration of a conserved nucleotide. The variant falls within a highly conserved EGF-like calcium binding ... (more)
Pathogenic
(Nov 01, 2016)
criteria provided, single submitter
Method: clinical testing
Marfan syndrome
Allele origin: germline
Center for Human Genetics, Inc
Accession: SCV000781404.1
Submitted: (Dec 20, 2017)
Evidence details
Pathogenic
(Mar 28, 2018)
criteria provided, single submitter
Method: clinical testing
Marfan syndrome
Thoracic aortic aneurysm and aortic dissection
Allele origin: germline
Invitae
Accession: SCV000627974.3
Submitted: (Aug 29, 2018)
Evidence details
Publications
PubMed (9)
Comment:
This sequence change replaces isoleucine with threonine at codon 2269 of the FBN1 protein (p.Ile2269Thr). The isoleucine residue is highly conserved and there is a ... (more)
Likely pathogenic
(Sep 17, 2015)
criteria provided, single submitter
Method: clinical testing
cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000320238.4
Submitted: (Jul 30, 2018)
Evidence details
Publications
PubMed (4)
Comment:
Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved ... (more)
Likely pathogenic
(May 04, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000603655.2
Submitted: (Oct 10, 2018)
Evidence details
Comment:
The c.6806T>C; p.Ile2269Thr variant (rs193922228) has been reported in multiple individuals affected with Marfan syndrome or FBN1-related disorders (Attanasio 2008, Comeglio 2007, Katzke 2002, Liu ... (more)
Pathogenic
(Jul 12, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000322364.7
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The I2269T pathogenic variant in the FBN1 gene has been reported in multiple individuals with Marfan syndrome or features of Marfan syndrome, and was collectively ... (more)
Uncertain significance
(Nov 07, 2017)
no assertion criteria provided
Method: clinical testing
Marfan syndrome
Allele origin: germline
Center for Medical Genetics Ghent,University of Ghent
Accession: SCV000787271.1
Submitted: (Apr 25, 2018)
Evidence details

Citations for this variant

Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Genetic testing of 248 Chinese aortopathy patients using a panel assay. Yang H Scientific reports 2016 PMID: 27611364
Performant Mutation Identification Using Targeted Next-Generation Sequencing of 14 Thoracic Aortic Aneurysm Genes. Proost D Human mutation 2015 PMID: 25907466
The spectrum of FBN1, TGFβR1, TGFβR2 and ACTA2 variants in 594 individuals with suspected Marfan Syndrome, Loeys-Dietz Syndrome or Thoracic Aortic Aneurysms and Dissections (TAAD). Lerner-Ellis JP Molecular genetics and metabolism 2014 PMID: 24793577
Identification of the minimal combination of clinical features in probands for efficient mutation detection in the FBN1 gene. Stheneur C European journal of human genetics : EJHG 2009 PMID: 19293843
Prevalence of dural ectasia in 63 gene-mutation-positive patients with features of Marfan syndrome type 1 and Loeys-Dietz syndrome and report of 22 novel FBN1 mutations. Söylen B Clinical genetics 2009 PMID: 19159394
FBN1 mutation screening of patients with Marfan syndrome and related disorders: detection of 46 novel FBN1 mutations. Attanasio M Clinical genetics 2008 PMID: 18435798
The importance of mutation detection in Marfan syndrome and Marfan-related disorders: report of 193 FBN1 mutations. Comeglio P Human mutation 2007 PMID: 17657824
Marfan syndrome--a diagnostic challenge caused by phenotypic and genetic heterogeneity. Baumgartner C Methods of information in medicine 2005 PMID: 16342915
Update of the UMD-FBN1 mutation database and creation of an FBN1 polymorphism database. Collod-Béroud G Human mutation 2003 PMID: 12938084
TGGE screening of the entire FBN1 coding sequence in 126 individuals with marfan syndrome and related fibrillinopathies. Katzke S Human mutation 2002 PMID: 12203992
Denaturing HPLC-identified novel FBN1 mutations, polymorphisms, and sequence variants in Marfan syndrome and related connective tissue disorders. Liu WO Genetic testing 1997 PMID: 10464652

Record last updated Jun 24, 2019