NM_000138.5(FBN1):c.5823_5824del (p.Cys1942fs) AND Marfan syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 1, 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:: RCV000476231.3

Allele description [Variation Report for NM_000138.5(FBN1):c.5823_5824del (p.Cys1942fs)]

NM_000138.5(FBN1):c.5823_5824del (p.Cys1942fs)

Gene:

FBN1:fibrillin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_000138.5(FBN1):c.5823_5824del (p.Cys1942fs)

HGVS:

NC_000015.10:g.48445470_48445471del
NG_008805.2:g.205319_205320del
NM_000138.5:c.5823_5824delMANE SELECT
NP_000129.3:p.Cys1942fs
LRG_778t1:c.5823_5824del
LRG_778:g.205319_205320del
NC_000015.9:g.48737666_48737667del
NC_000015.9:g.48737667_48737668del
NM_000138.4:c.5823_5824del
NM_000138.4:c.5823_5824delTT

Protein change:

C1942fs

Links:

dbSNP: rs1060501089

NCBI 1000 Genomes Browser:

rs1060501089

Molecular consequence:

NM_000138.5:c.5823_5824del - 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

Recent activity

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Mus musculus RAD51-like 3 (S. cerevisiae) (Rad51l3), mRNA
Mus musculus RAD51-like 3 (S. cerevisiae) (Rad51l3), mRNA
gi|6755277|ref|NM_011235.1|

Nucleotide
Mus musculus polymerase (DNA directed), kappa (Polk), transcript variant a, mRNA
Mus musculus polymerase (DNA directed), kappa (Polk), transcript variant a, mRNA
gi|1109516628|ref|NM_012048.3|

Nucleotide
Homo sapiens dickkopf WNT signaling pathway inhibitor 1 (DKK1), mRNA
Homo sapiens dickkopf WNT signaling pathway inhibitor 1 (DKK1), mRNA
gi|1519242912|ref|NM_012242.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000544941	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 12, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002025363	Centre of Medical Genetics, University of Antwerp	criteria provided, single submitter (Submitter's publication)	Pathogenic (Mar 1, 2021)	unknown	research	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000544941

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 12, 2016)

germline

clinical testing

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

SCV002025363

Centre of Medical Genetics, University of Antwerp

criteria provided, single submitter

(Submitter's publication)

Pathogenic
(Mar 1, 2021)

unknown

research

Citation Link

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
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000544941.2

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

Description

This sequence change deletes 2 nucleotides from exon 48 of the FBN1 mRNA (c.5823_5824delTT), causing a frameshift at codon 1942. This creates a premature translational stop signal (p.Cys1942Glnfs*7) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). For these reasons, this variant has been classified as Pathogenic.

#	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

From Centre of Medical Genetics, University of Antwerp, SCV002025363.1

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

Description

PM2, PVS1, 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

Last Updated: Sep 29, 2024

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