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NM_000138.5(FBN1):c.4621C>T (p.Arg1541Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 5, 2024
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:
RCV000462664.10

Allele description [Variation Report for NM_000138.5(FBN1):c.4621C>T (p.Arg1541Ter)]

NM_000138.5(FBN1):c.4621C>T (p.Arg1541Ter)

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.4621C>T (p.Arg1541Ter)
Other names:
p.R1541X:CGA>TGA
HGVS:
  • NC_000015.10:g.48468064G>A
  • NG_008805.2:g.182725C>T
  • NM_000138.5:c.4621C>TMANE SELECT
  • NP_000129.3:p.Arg1541Ter
  • NP_000129.3:p.Arg1541Ter
  • LRG_778t1:c.4621C>T
  • LRG_778:g.182725C>T
  • LRG_778p1:p.Arg1541Ter
  • NC_000015.9:g.48760261G>A
  • NM_000138.4:c.4621C>T
Protein change:
R1541*
Links:
dbSNP: rs794728228
NCBI 1000 Genomes Browser:
rs794728228
Molecular consequence:
  • NM_000138.5:c.4621C>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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000544836Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 5, 2024)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

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

Stheneur C, Collod-BĂ©roud 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

Molecular analysis of eight mutations in FBN1.

Halliday D, Hutchinson S, Kettle S, Firth H, Wordsworth P, Handford PA.

Hum Genet. 1999 Dec;105(6):587-97.

PubMed [citation]
PMID:
10647894
See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000544836.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change creates a premature translational stop signal (p.Arg1541*) 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 is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Marfan syndrome (PMID: 10647894, 11933199, 12161601, 12700307, 16222657, 17657824, 23684891). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 200052). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024