NM_000138.5(FBN1):c.4583-5A>G AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 15, 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:: RCV000458795.7

Allele description [Variation Report for NM_000138.5(FBN1):c.4583-5A>G]

NM_000138.5(FBN1):c.4583-5A>G

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.4583-5A>G

HGVS:

NC_000015.10:g.48468107T>C
NG_008805.2:g.182682A>G
NM_000138.5:c.4583-5A>GMANE SELECT
LRG_778t1:c.4583-5A>G
LRG_778:g.182682A>G
NC_000015.9:g.48760304T>C
NM_000138.4:c.4583-5A>G

Links:

dbSNP: rs778966916

NCBI 1000 Genomes Browser:

rs778966916

Molecular consequence:

NM_000138.5:c.4583-5A>G - intron variant - [Sequence Ontology: SO:0001627]

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

Name:: Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:: Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:: MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000544901	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 15, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25101912, 25652356, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000544901

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 15, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Increased frequency of FBN1 truncating and splicing variants in Marfan syndrome patients with aortic events.

Baudhuin LM, Kotzer KE, Lagerstedt SA.

Genet Med. 2015 Mar;17(3):177-87. doi: 10.1038/gim.2014.91. Epub 2014 Aug 7.

PubMed [citation]

PMID:: 25101912

Decreased frequency of FBN1 missense variants in Ghent criteria-positive Marfan syndrome and characterization of novel FBN1 variants.

Baudhuin LM, Kotzer KE, Lagerstedt SA.

J Hum Genet. 2015 May;60(5):241-52. doi: 10.1038/jhg.2015.10. Epub 2015 Feb 5.

PubMed [citation]

PMID:: 25652356

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000544901.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change falls in intron 37 of the FBN1 mRNA. It does not directly change the encoded amino acid sequence of the FBN1 protein. This variant is not present in population databases (ExAC no frequency). In summary this is a rare intronic variant that is predicted to affect protein splicing and has been reported as de novo in an affected individual. For these reasons, this variant has ben classified as Likely Pathogenic. Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this intronic variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. This sequence change was reported as de novo in an individual affected with Marfan syndrome (PMID: 25101912, 25652356).

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine