NM_000138.5(FBN1):c.4096G>A (p.Glu1366Lys) AND Marfan syndrome

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Mar 12, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000663695.4

Allele description [Variation Report for NM_000138.5(FBN1):c.4096G>A (p.Glu1366Lys)]

NM_000138.5(FBN1):c.4096G>A (p.Glu1366Lys)

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.4096G>A (p.Glu1366Lys)

Other names:

p.E1366K:GAA>AAA; p.Glu1366Lys

HGVS:

NC_000015.10:g.48474369C>T
NG_008805.2:g.176420G>A
NM_000138.5:c.4096G>AMANE SELECT
NP_000129.3:p.Glu1366Lys
NP_000129.3:p.Glu1366Lys
LRG_778t1:c.4096G>A
LRG_778:g.176420G>A
LRG_778p1:p.Glu1366Lys
NC_000015.9:g.48766566C>T
NM_000138.4:c.4096G>A

Protein change:

E1366K

Links:

dbSNP: rs763449629

NCBI 1000 Genomes Browser:

rs763449629

Molecular consequence:

NM_000138.5:c.4096G>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000787027	Center for Medical Genetics Ghent, University of Ghent	no assertion criteria provided	Likely pathogenic (Nov 7, 2017)	germline	clinical testing
SCV002025298	Centre of Medical Genetics, University of Antwerp	criteria provided, single submitter (Submitter's publication)	Likely pathogenic (Mar 1, 2021)	unknown	research	Citation Link,
SCV005088885	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 12, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000787027

Center for Medical Genetics Ghent, University of Ghent

no assertion criteria provided

Likely pathogenic
(Nov 7, 2017)

germline

clinical testing

SCV002025298

Centre of Medical Genetics, University of Antwerp

criteria provided, single submitter

(Submitter's publication)

Likely pathogenic
(Mar 1, 2021)

unknown

research

Citation Link,

SCV005088885

Breakthrough Genomics, Breakthrough Genomics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 12, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Center for Medical Genetics Ghent, University of Ghent, SCV000787027.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Centre of Medical Genetics, University of Antwerp, SCV002025298.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

Description

PM2, PS6, PP4

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Breakthrough Genomics, Breakthrough Genomics, SCV005088885.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant is predicted to be damaging by insilico missense prediction tools (SIFT and Polyphen2). It was previously reported in multiple patients with Marfan syndrome [PMID: 14695540, 27611364, 27724990, 24199744, 17657824] and reported to affect calcium-binding EGF-like module [PMID: 14695540, 27611364].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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