NM_000138.5(FBN1):c.1737del (p.Asn580fs) AND Marfan syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 10, 2023
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:: RCV003447674.1

Allele description [Variation Report for NM_000138.5(FBN1):c.1737del (p.Asn580fs)]

NM_000138.5(FBN1):c.1737del (p.Asn580fs)

Gene:

FBN1:fibrillin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_000138.5(FBN1):c.1737del (p.Asn580fs)

HGVS:

NC_000015.10:g.48508683del
NG_008805.2:g.142107del
NM_000138.5:c.1737delMANE SELECT
NM_001406716.1:c.1737del
NP_000129.3:p.Asn580Thrfs
NP_000129.3:p.Asn580fs
NP_001393645.1:p.Asn580fs
LRG_778t1:c.1736del
LRG_778:g.142107del
LRG_778p1:p.Asn580Thrfs
NC_000015.9:g.48800880del
NM_000138.4:c.1736delG
NM_000138.5:c.1737delGMANE SELECT

Protein change:

N580fs

Molecular consequence:

NM_000138.5:c.1737del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406716.1:c.1737del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004175225	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 10, 2023)	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

SCV004175225

Genetics and Molecular Pathology, SA Pathology

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 10, 2023)

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

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 Genetics and Molecular Pathology, SA Pathology, SCV004175225.1

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

Description

The FBN1 c.1737del variant is classified as a LIKELY PATHOGENIC (PVS1, PM2) The variant is a single-base pair deletion in exon 15/66 of the FBN1 gene, which is predicted to result in a frameshift starting with codon Asparagine 580, changes this amino acid to a Threonine residue, and creates a premature STOP codon 45 amino acids downstream, denoted p.N580TfsX45. This variant is predicted to cause loss of normal protein function which is a known disease causing mehanism of Marfan syndrome in the FBN1 gene (PVS1). The variant is not in dbSNP and is absent from population databases (PM2). The variant has not been reported in ClinVar or HGMD.

#	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: Dec 17, 2023

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