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NM_000138.5(FBN1):c.1090C>T (p.Arg364Ter) AND Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 11, 2020
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:
RCV001175536.8

Allele description [Variation Report for NM_000138.5(FBN1):c.1090C>T (p.Arg364Ter)]

NM_000138.5(FBN1):c.1090C>T (p.Arg364Ter)

Genes:
LOC113939944:Sharpr-MPRA regulatory region 9539 [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.1090C>T (p.Arg364Ter)
Other names:
p.R364X:CGA>TGA
HGVS:
  • NC_000015.10:g.48520716G>A
  • NG_008805.2:g.130073C>T
  • NG_063729.1:g.285G>A
  • NM_000138.5:c.1090C>TMANE SELECT
  • NP_000129.3:p.Arg364Ter
  • NP_000129.3:p.Arg364Ter
  • LRG_778t1:c.1090C>T
  • LRG_778:g.130073C>T
  • LRG_778p1:p.Arg364Ter
  • NC_000015.9:g.48812913G>A
  • NM_000138.4:c.1090C>T
  • p.Arg364*
Protein change:
R364*
Links:
dbSNP: rs794728165
NCBI 1000 Genomes Browser:
rs794728165
Molecular consequence:
  • NM_000138.5:c.1090C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections
Identifiers:
MedGen: CN229799

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001339152Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Mar 11, 2020) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Update of the UMD-FBN1 mutation database and creation of an FBN1 polymorphism database.

Collod-Béroud G, Le Bourdelles S, Ades L, Ala-Kokko L, Booms P, Boxer M, Child A, Comeglio P, De Paepe A, Hyland JC, Holman K, Kaitila I, Loeys B, Matyas G, Nuytinck L, Peltonen L, Rantamaki T, Robinson P, Steinmann B, Junien C, Béroud C, Boileau C.

Hum Mutat. 2003 Sep;22(3):199-208. Review.

PubMed [citation]
PMID:
12938084

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
See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001339152.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Variant summary: FBN1 c.1090C>T (p.Arg364X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251536 control chromosomes(gnomAD). c.1090C>T has been reported in the literature in multiple individuals affected with Marfan Syndrome (e.g. Collod-Beroud_2003, Weerakkody_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Dec 22, 2024