NM_000138.5(FBN1):c.5863C>T (p.Gln1955Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 15, 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:: RCV001852714.6

Allele description [Variation Report for NM_000138.5(FBN1):c.5863C>T (p.Gln1955Ter)]

NM_000138.5(FBN1):c.5863C>T (p.Gln1955Ter)

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.5863C>T (p.Gln1955Ter)

Other names:

p.Q1955X:CAG>TAG

HGVS:

NC_000015.10:g.48445430G>A
NG_008805.2:g.205359C>T
NM_000138.5:c.5863C>TMANE SELECT
NP_000129.3:p.Gln1955Ter
NP_000129.3:p.Gln1955Ter
LRG_778t1:c.5863C>T
LRG_778:g.205359C>T
LRG_778p1:p.Gln1955Ter
NC_000015.9:g.48737627G>A
NM_000138.4:c.5863C>T
c.5863C>T
p.Gln1955X

Protein change:

Q1955*

Links:

dbSNP: rs363807

NCBI 1000 Genomes Browser:

rs363807

Molecular consequence:

NM_000138.5:c.5863C>T - 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

Recent activity

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peripheral inner membrane phage-shock protein [Yersinia pestis KIM10+]
peripheral inner membrane phage-shock protein [Yersinia pestis KIM10+]
gi|22125875|ref|NP_669298.1|

Protein
LOW QUALITY PROTEIN: natural resistance-associated macrophage protein 1 [Apteryx...
LOW QUALITY PROTEIN: natural resistance-associated macrophage protein 1 [Apteryx mantelli]
gi|2788398917|ref|XP_067155309.1|

Protein
Homo sapiens muskelin 1 (MKLN1), transcript variant 2, mRNA
Homo sapiens muskelin 1 (MKLN1), transcript variant 2, mRNA
gi|1519241947|ref|NM_013255.5|

Nucleotide
Patchy sclerosis of the proximal phalanx of the thumb
Patchy sclerosis of the proximal phalanx of the thumb

MedGen
Sclerosis of the distal phalanx of the thumb
Sclerosis of the distal phalanx of the thumb

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002244440	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 15, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 12068374, 22772377, 24793577, 17657824, 19293843, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002244440

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 15, 2022)

germline

clinical testing

PubMed (6)
[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

Premature termination mutations in FBN1: distinct effects on differential allelic expression and on protein and clinical phenotypes.

Schrijver I, Liu W, Odom R, Brenn T, Oefner P, Furthmayr H, Francke U.

Am J Hum Genet. 2002 Aug;71(2):223-37. Epub 2002 Jun 14.

PubMed [citation]

PMID:: 12068374
PMCID:: PMC379156

Exon 47 skipping of fibrillin-1 leads preferentially to cardiovascular defects in patients with thoracic aortic aneurysms and dissections.

Wang WJ, Han P, Zheng J, Hu FY, Zhu Y, Xie JS, Guo J, Zhang Z, Dong J, Zheng GY, Cao H, Liu TS, Fu Q, Sun L, Yang BB, Tian XL.

J Mol Med (Berl). 2013 Jan;91(1):37-47. doi: 10.1007/s00109-012-0931-y. Epub 2012 Jul 8.

PubMed [citation]

PMID:: 22772377

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002244440.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 42393). This premature translational stop signal has been observed in individual(s) with Marfan syndrome (PMID: 12068374, 22772377, 24793577). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1955*) 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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