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NM_000138.5(FBN1):c.4466A>G (p.Asn1489Ser) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 14, 2021
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:
RCV000631906.6

Allele description [Variation Report for NM_000138.5(FBN1):c.4466A>G (p.Asn1489Ser)]

NM_000138.5(FBN1):c.4466A>G (p.Asn1489Ser)

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.4466A>G (p.Asn1489Ser)
Other names:
NM_000138.5(FBN1):c.4466A>G; p.Asn1489Ser
HGVS:
  • NC_000015.10:g.48468528T>C
  • NG_008805.2:g.182261A>G
  • NM_000138.5:c.4466A>GMANE SELECT
  • NP_000129.3:p.Asn1489Ser
  • NP_000129.3:p.Asn1489Ser
  • LRG_778t1:c.4466A>G
  • LRG_778:g.182261A>G
  • LRG_778p1:p.Asn1489Ser
  • NC_000015.9:g.48760725T>C
  • NM_000138.4:c.4466A>G
Protein change:
N1489S
Links:
dbSNP: rs1057518501
NCBI 1000 Genomes Browser:
rs1057518501
Molecular consequence:
  • NM_000138.5:c.4466A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000753009Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 14, 2021) 		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

FBN1 mutations in patients with descending thoracic aortic dissections.

Brautbar A, LeMaire SA, Franco LM, Coselli JS, Milewicz DM, Belmont JW.

Am J Med Genet A. 2010 Feb;152A(2):413-6. doi: 10.1002/ajmg.a.32856.

PubMed [citation]
PMID:
20082464
PMCID:
PMC3593235

Applying massive parallel sequencing to molecular diagnosis of Marfan and Loeys-Dietz syndromes.

Baetens M, Van Laer L, De Leeneer K, Hellemans J, De Schrijver J, Van De Voorde H, Renard M, Dietz H, Lacro RV, Menten B, Van Criekinge W, De Backer J, De Paepe A, Loeys B, Coucke PJ.

Hum Mutat. 2011 Sep;32(9):1053-62. doi: 10.1002/humu.21525. Epub 2011 Jul 20.

PubMed [citation]
PMID:
21542060
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000753009.3

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

Description

This sequence change replaces asparagine with serine at codon 1489 of the FBN1 protein (p.Asn1489Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 373598). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant disrupts the p.Asn1489 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been observed in individuals with FBN1-related conditions (PMID: 20082464, 21542060, 26621581), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024