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NM_000138.5(FBN1):c.5885A>G (p.Tyr1962Cys) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 15, 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:
RCV002352138.2

Allele description [Variation Report for NM_000138.5(FBN1):c.5885A>G (p.Tyr1962Cys)]

NM_000138.5(FBN1):c.5885A>G (p.Tyr1962Cys)

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.5885A>G (p.Tyr1962Cys)
Other names:
NM_000138.5(FBN1):c.5885A>G; p.Tyr1962Cys
HGVS:
  • NC_000015.10:g.48445408T>C
  • NG_008805.2:g.205381A>G
  • NM_000138.5:c.5885A>GMANE SELECT
  • NP_000129.3:p.Tyr1962Cys
  • NP_000129.3:p.Tyr1962Cys
  • LRG_778t1:c.5885A>G
  • LRG_778:g.205381A>G
  • LRG_778p1:p.Tyr1962Cys
  • NC_000015.9:g.48737605T>C
  • NM_000138.4:c.5885A>G
Protein change:
Y1962C
Links:
dbSNP: rs1346043320
NCBI 1000 Genomes Browser:
rs1346043320
Molecular consequence:
  • NM_000138.5:c.5885A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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
SCV002652833Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Apr 15, 2021) 		germlineclinical testing

PubMed (5)
[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

Consequences of cysteine mutations in calcium-binding epidermal growth factor modules of fibrillin-1.

Vollbrandt T, Tiedemann K, El-Hallous E, Lin G, Brinckmann J, John H, Bätge B, Notbohm H, Reinhardt DP.

J Biol Chem. 2004 Jul 30;279(31):32924-31. Epub 2004 May 25.

PubMed [citation]
PMID:
15161917

The molecular genetics of Marfan syndrome and related disorders.

Robinson PN, Arteaga-Solis E, Baldock C, Collod-Béroud G, Booms P, De Paepe A, Dietz HC, Guo G, Handford PA, Judge DP, Kielty CM, Loeys B, Milewicz DM, Ney A, Ramirez F, Reinhardt DP, Tiedemann K, Whiteman P, Godfrey M.

J Med Genet. 2006 Oct;43(10):769-87. Epub 2006 Mar 29. Review.

PubMed [citation]
PMID:
16571647
PMCID:
PMC2563177
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002652833.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The p.Y1962C variant (also known as c.5885A>G), located in coding exon 47 of the FBN1 gene, results from an A to G substitution at nucleotide position 5885. The tyrosine at codon 1962 is replaced by cysteine, an amino acid with highly dissimilar properties, and is located in the cbEGF-like #29 domain. The majority of FBN1 mutations identified to date have involved the substitution or generation of cysteine residues within cbEGF domains (Vollbrandt T et al. J Biol Chem. 2004;279(31):32924-32931). This variant has been detected in an individual reported to have Marfan syndrome; however, details were limited (Somers AE et al. Am J Med Genet A, 2016 07;170:1786-90). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Oct 8, 2024