NM_000138.5(FBN1):c.6145del (p.Ser2049fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 14, 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:: RCV003795211.2

Allele description [Variation Report for NM_000138.5(FBN1):c.6145del (p.Ser2049fs)]

NM_000138.5(FBN1):c.6145del (p.Ser2049fs)

Gene:

FBN1:fibrillin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_000138.5(FBN1):c.6145del (p.Ser2049fs)

HGVS:

NC_000015.10:g.48441739del
NG_008805.2:g.209050del
NM_000138.5:c.6145delMANE SELECT
NM_001406716.1:c.6145del
NP_000129.3:p.Ser2049Valfs
NP_000129.3:p.Ser2049fs
NP_001393645.1:p.Ser2049fs
LRG_778t1:c.6145del
LRG_778:g.209050del
LRG_778p1:p.Ser2049Valfs
NC_000015.9:g.48733936del
NM_000138.4:c.6145delA

Protein change:

S2049fs

Molecular consequence:

NM_000138.5:c.6145del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406716.1:c.6145del - 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
SCV004590204	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 14, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17657824, 19293843, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004590204

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 14, 2022)

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

The importance of mutation detection in Marfan syndrome and Marfan-related disorders: report of 193 FBN1 mutations.

Comeglio P, Johnson P, Arno G, Brice G, Evans A, Aragon-Martin J, da Silva FP, Kiotsekoglou A, Child A.

Hum Mutat. 2007 Sep;28(9):928.

PubMed [citation]

PMID:: 17657824

Identification of the minimal combination of clinical features in probands for efficient mutation detection in the FBN1 gene.

Stheneur C, Collod-Béroud G, Faivre L, Buyck JF, Gouya L, Le Parc JM, Moura B, Muti C, Grandchamp B, Sultan G, Claustres M, Aegerter P, Chevallier B, Jondeau G, Boileau C.

Eur J Hum Genet. 2009 Sep;17(9):1121-8. doi: 10.1038/ejhg.2009.36. Epub 2009 Mar 18.

PubMed [citation]

PMID:: 19293843
PMCID:: PMC2986588

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004590204.1

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser2049Valfs*10) 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). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. 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

Last Updated: Sep 29, 2024

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