NM_000138.5(FBN1):c.2963G>A (p.Trp988Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 4, 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:: RCV001941571.6

Allele description [Variation Report for NM_000138.5(FBN1):c.2963G>A (p.Trp988Ter)]

NM_000138.5(FBN1):c.2963G>A (p.Trp988Ter)

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.2963G>A (p.Trp988Ter)

HGVS:

NC_000015.10:g.48489970C>T
NG_008805.2:g.160819G>A
NM_000138.5:c.2963G>AMANE SELECT
NP_000129.3:p.Trp988Ter
LRG_778t1:c.2963G>A
LRG_778:g.160819G>A
NC_000015.9:g.48782167C>T
NM_000138.4:c.2963G>A

Protein change:

W988*

Links:

dbSNP: rs2043543553

NCBI 1000 Genomes Browser:

rs2043543553

Molecular consequence:

NM_000138.5:c.2963G>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002228192	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 4, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 26410935, 27724990, 17657824, 19293843, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002228192

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 4, 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

[Clinical and Genetic Characteristics of Russian Marfan Patients].

Semyachkina AN, Adyan TA, Khabadze MN, Novikov PV, Polyakov AV.

Genetika. 2015 Jul;51(7):812-20. Russian.

PubMed [citation]

PMID:: 26410935

Identification of FBN1 gene mutations in Ukrainian Marfan syndrome patients.

Zhurayev R, Proost D, Zerbino D, Fedorenko V, Meester JA, VAN Laer L, Loeys BL.

Genet Res (Camb). 2016 Oct 11;98:e13.

PubMed [citation]

PMID:: 27724990
PMCID:: PMC6865158

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002228192.3

#	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. This premature translational stop signal has been observed in individuals with Marfan syndrome (PMID: 26410935, 27724990). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp988*) 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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