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NM_000138.4(FBN1):c.4096G>A (p.Glu1366Lys)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5 (Most recent: Jan 7, 2021)
Last evaluated:
Sep 1, 2020
Accession:
VCV000200036.6
Variation ID:
200036
Description:
single nucleotide variant
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NM_000138.4(FBN1):c.4096G>A (p.Glu1366Lys)

Allele ID
197710
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q21.1
Genomic location
15: 48474369 (GRCh38) GRCh38 UCSC
15: 48766566 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_778:g.176420G>A
NC_000015.10:g.48474369C>T
NC_000015.9:g.48766566C>T
... more HGVS
Protein change
E1366K
Other names
p.E1366K:GAA>AAA
Canonical SPDI
NC_000015.10:48474368:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
dbSNP: rs763449629
ClinGen: CA014760
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Nov 15, 2018 RCV000181508.2
Pathogenic 1 criteria provided, single submitter Jul 11, 2016 RCV000588449.1
Likely pathogenic 1 criteria provided, single submitter Feb 28, 2018 RCV000770671.2
Pathogenic 1 criteria provided, single submitter Sep 1, 2020 RCV001224814.2
Likely pathogenic 1 no assertion criteria provided Nov 7, 2017 RCV000663695.1
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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
4774 4869

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jul 11, 2016)
criteria provided, single submitter
Method: clinical testing
Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695533.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (6)
Comment:
Variant summary: The c.4096G>A (p.Glu1366Lys) in FBN1 gene is a missense change that involves a highly conserved nucleotide and 3/4 in silico tools predict deleterious … (more)
Likely pathogenic
(Feb 28, 2018)
criteria provided, single submitter
Method: clinical testing
Familial thoracic aortic aneurysm and aortic dissection
Allele origin: germline
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario
Accession: SCV000902130.2
Submitted: (Mar 03, 2020)
Evidence details
Pathogenic
(Sep 01, 2020)
criteria provided, single submitter
Method: clinical testing
Marfan syndrome
Familial thoracic aortic aneurysm and aortic dissection
Allele origin: germline
Invitae
Accession: SCV001397037.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change replaces glutamic acid with lysine at codon 1366 of the FBN1 protein (p.Glu1366Lys). The glutamic acid residue is highly conserved and there … (more)
Likely pathogenic
(Nov 15, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000233811.11
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The E1366K variant has been reported in individuals with a clinical diagnosis or suspected diagnosis of Marfan syndrome (Biggin A et al., 2004; Comeglio et … (more)
Likely pathogenic
(Nov 07, 2017)
no assertion criteria provided
Method: clinical testing
Marfan syndrome
Allele origin: germline
Center for Medical Genetics Ghent,University of Ghent
Accession: SCV000787027.1
Submitted: (Apr 25, 2018)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Application of next-generation sequencing to screen for pathogenic mutations in 123 unrelated Chinese patients with Marfan syndrome or a related disease. Li J Science China. Life sciences 2019 PMID: 31098894
Identification of FBN1 gene mutations in Ukrainian Marfan syndrome patients. Zhurayev R Genetics research 2016 PMID: 27724990
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
Detection of 15 novel mutations in 52 children from 40 families with the Marfan or Loeys-Dietz syndrome and phenotype-genotype correlations. Pees C Clinical genetics 2014 PMID: 24199744
Systematic screening of FBN1 gene unclassified missense variants for splice abnormalities. Robinson DO Clinical genetics 2012 PMID: 21895641
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
Detection of thirty novel FBN1 mutations in patients with Marfan syndrome or a related fibrillinopathy. Biggin A Human mutation 2004 PMID: 14695540

Text-mined citations for rs763449629...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 14, 2021