NM_000138.5(FBN1):c.5817del (p.Asn1940fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 1, 2022
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:: RCV001852287.4

Allele description [Variation Report for NM_000138.5(FBN1):c.5817del (p.Asn1940fs)]

NM_000138.5(FBN1):c.5817del (p.Asn1940fs)

Gene:

FBN1:fibrillin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_000138.5(FBN1):c.5817del (p.Asn1940fs)

HGVS:

NC_000015.10:g.48445478del
NG_008805.2:g.205313del
NM_000138.5:c.5817delMANE SELECT
NP_000129.3:p.Asn1940fs
LRG_778:g.205313del
NC_000015.9:g.48737673del
NC_000015.9:g.48737675del
NM_000138.4:c.5817delG
p.N1940IfsX40

Protein change:

N1940fs

Links:

dbSNP: rs794728311

NCBI 1000 Genomes Browser:

rs794728311

Molecular consequence:

NM_000138.5:c.5817del - 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

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002242607	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 1, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19159394, 32679894, 17657824, 19293843, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002242607

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 1, 2022)

germline

clinical testing

PubMed (5)
[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

Prevalence of dural ectasia in 63 gene-mutation-positive patients with features of Marfan syndrome type 1 and Loeys-Dietz syndrome and report of 22 novel FBN1 mutations.

Söylen B, Singh KK, Abuzainin A, Rommel K, Becker H, Arslan-Kirchner M, Schmidtke J.

Clin Genet. 2009 Mar;75(3):265-70. doi: 10.1111/j.1399-0004.2008.01126.x. Epub 2009 Jan 20.

PubMed [citation]

PMID:: 19159394

Genotype-Phenotype Correlation in Children: The Impact of FBN1 Variants on Pediatric Marfan Care.

Stark VC, Hensen F, Kutsche K, Kortüm F, Olfe J, Wiegand P, von Kodolitsch Y, Kozlik-Feldmann R, Müller GC, Mir TS.

Genes (Basel). 2020 Jul 15;11(7). doi:pii: E799. 10.3390/genes11070799.

PubMed [citation]

PMID:: 32679894
PMCID:: PMC7397236

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002242607.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 200163). This premature translational stop signal has been observed in individuals with Marfan syndrome (PMID: 19159394, 32679894). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn1940Ilefs*40) in the FBN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843).

#	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

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