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NM_000138.5(FBN1):c.994C>T (p.Arg332Cys) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 10, 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:
RCV002379965.2

Allele description [Variation Report for NM_000138.5(FBN1):c.994C>T (p.Arg332Cys)]

NM_000138.5(FBN1):c.994C>T (p.Arg332Cys)

Genes:
LOC113939944:Sharpr-MPRA regulatory region 9539 [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.994C>T (p.Arg332Cys)
HGVS:
  • NC_000015.10:g.48520812G>A
  • NG_008805.2:g.129977C>T
  • NG_063729.1:g.381G>A
  • NM_000138.5:c.994C>TMANE SELECT
  • NP_000129.3:p.Arg332Cys
  • LRG_778t1:c.994C>T
  • LRG_778:g.129977C>T
  • NC_000015.9:g.48813009G>A
  • NM_000138.4:c.994C>T
  • p.Arg332Cys
Protein change:
R332C
Links:
dbSNP: rs1161109360
NCBI 1000 Genomes Browser:
rs1161109360
Molecular consequence:
  • NM_000138.5:c.994C>T - 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
SCV002694384Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Feb 10, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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Summary from all submissions

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

Citations

PubMed

FBN1 mutations largely contribute to sporadic non-syndromic aortic dissection.

Tan L, Li Z, Zhou C, Cao Y, Zhang L, Li X, Cianflone K, Wang Y, Wang DW.

Hum Mol Genet. 2017 Dec 15;26(24):4814-4822. doi: 10.1093/hmg/ddx360.

PubMed [citation]
PMID:
28973303

Details of each submission

From Ambry Genetics, SCV002694384.2

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

Description

The p.R332C variant (also known as c.994C>T), located in coding exon 9 of the FBN1 gene, results from a C to T substitution at nucleotide position 994. The arginine at codon 332 is replaced by cysteine, an amino acid with highly dissimilar properties, and is located in the TGFBP #01 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 reported in an individual with sporadic, non-syndromic subclavian aortic dissection (Tan L et al. Hum Mol Genet, 2017 12;26:4814-4822). 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 20, 2024