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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002244440Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 15, 2022) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024