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NM_000138.5(FBN1):c.4467T>A (p.Asn1489Lys) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 6, 2023
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:
RCV001046640.13

Allele description [Variation Report for NM_000138.5(FBN1):c.4467T>A (p.Asn1489Lys)]

NM_000138.5(FBN1):c.4467T>A (p.Asn1489Lys)

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.4467T>A (p.Asn1489Lys)
HGVS:
  • NC_000015.10:g.48468527A>T
  • NG_008805.2:g.182262T>A
  • NM_000138.5:c.4467T>AMANE SELECT
  • NP_000129.3:p.Asn1489Lys
  • NP_000129.3:p.Asn1489Lys
  • LRG_778t1:c.4467T>A
  • LRG_778:g.182262T>A
  • LRG_778p1:p.Asn1489Lys
  • NC_000015.9:g.48760724A>T
  • NM_000138.4:c.4467T>A
  • c.4467T>A
Protein change:
N1489K
Links:
dbSNP: rs193922205
NCBI 1000 Genomes Browser:
rs193922205
Molecular consequence:
  • NM_000138.5:c.4467T>A - 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
SCV001210551Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 6, 2023) 		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 Invitae, SCV001210551.5

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

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN1 protein function. ClinVar contains an entry for this variant (Variation ID: 36076). This missense change has been observed in individuals with thoracic aortic aneurysm and dissection (PMID: 20082464, 21542060, 26621581; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1489 of the FBN1 protein (p.Asn1489Lys).

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

Last Updated: Jun 2, 2024