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NM_000138.5(FBN1):c.8326C>T (p.Arg2776Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 26, 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:
RCV000631918.14

Allele description [Variation Report for NM_000138.5(FBN1):c.8326C>T (p.Arg2776Ter)]

NM_000138.5(FBN1):c.8326C>T (p.Arg2776Ter)

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.8326C>T (p.Arg2776Ter)
Other names:
p.R2776X:CGA>TGA
HGVS:
  • NC_000015.10:g.48411280G>A
  • NG_008805.2:g.239509C>T
  • NM_000138.5:c.8326C>TMANE SELECT
  • NP_000129.3:p.Arg2776Ter
  • NP_000129.3:p.Arg2776Ter
  • LRG_778t1:c.8326C>T
  • LRG_778:g.239509C>T
  • LRG_778p1:p.Arg2776Ter
  • NC_000015.9:g.48703477G>A
  • NM_000138.4:c.8326C>T
  • NM_000138.5:c.8326C>T
  • p.Arg2776X
  • p.R2776*
Protein change:
R2776*; ARG2776TER
Links:
OMIM: 134797.0017; dbSNP: rs137854466
NCBI 1000 Genomes Browser:
rs137854466
Molecular consequence:
  • NM_000138.5:c.8326C>T - nonsense - [Sequence Ontology: SO:0001587]
Functional consequence:
variation affecting protein [Variation Ontology: 0002]

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
SCV000753021Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 26, 2022) 		germlineclinical testing

PubMed (4)
[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

Identification of a novel nonsense mutation in the fibrillin gene (FBN1) using nonisotopic techniques.

Hayward C, Porteous ME, Brock DJ.

Hum Mutat. 1994;3(2):159-62. No abstract available.

PubMed [citation]
PMID:
7911051

Mutation screening of all 65 exons of the fibrillin-1 gene in 60 patients with Marfan syndrome: report of 12 novel mutations.

Hayward C, Porteous ME, Brock DJ.

Hum Mutat. 1997;10(4):280-9.

PubMed [citation]
PMID:
9338581
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000753021.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the FBN1 protein in which other variant(s) (p.Leu2854Profs*9, p.Gln2830*, p.Leu2854Profs*9) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 16439). This premature translational stop signal has been observed in individual(s) with FBN-1 related conditions (PMID: 7911051, 9338581, 11826022). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg2776*) in the FBN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 96 amino acid(s) of the FBN1 protein.

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

Last Updated: Apr 20, 2024