NM_000138.5(FBN1):c.184C>T (p.Arg62Cys) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 26, 2018
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:
RCV002313727.10

Allele description [Variation Report for NM_000138.5(FBN1):c.184C>T (p.Arg62Cys)]

NM_000138.5(FBN1):c.184C>T (p.Arg62Cys)

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.184C>T (p.Arg62Cys)
HGVS:
  • NC_000015.10:g.48613073G>A
  • NG_008805.2:g.37716C>T
  • NM_000138.5:c.184C>TMANE SELECT
  • NP_000129.3:p.Arg62Cys
  • NP_000129.3:p.Arg62Cys
  • LRG_778t1:c.184C>T
  • LRG_778:g.37716C>T
  • LRG_778p1:p.Arg62Cys
  • NC_000015.9:g.48905270G>A
  • NM_000138.4:c.184C>T
  • c.184C>T
Protein change:
R62C
Links:
dbSNP: rs25403
NCBI 1000 Genomes Browser:
rs25403
Molecular consequence:
  • NM_000138.5:c.184C>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
SCV000738849Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Feb 26, 2018) 		germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Sensitivity of conformation sensitive gel electrophoresis in detecting mutations in Marfan syndrome and related conditions.

Körkkö J, Kaitila I, Lönnqvist L, Peltonen L, Ala-Kokko L.

J Med Genet. 2002 Jan;39(1):34-41.

PubMed [citation]
PMID:
11826022
PMCID:
PMC1734965

TGGE screening of the entire FBN1 coding sequence in 126 individuals with marfan syndrome and related fibrillinopathies.

Katzke S, Booms P, Tiecke F, Palz M, Pletschacher A, Türkmen S, Neumann LM, Pregla R, Leitner C, Schramm C, Lorenz P, Hagemeier C, Fuchs J, Skovby F, Rosenberg T, Robinson PN.

Hum Mutat. 2002 Sep;20(3):197-208.

PubMed [citation]
PMID:
12203992
See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV000738849.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

The p.R62C pathogenic mutation (also known as c.184C>T), located in coding exon 2 of the FBN1 gene, results from a C to T substitution at nucleotide position 184. The arginine at codon 62 is replaced by cysteine, an amino acid with highly dissimilar properties, and is located in the 4-cys motif LTBP-like domain near the cb EGF-like #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 alteration has been reported in several patients with ectopia lentis and Marfan syndrome, and in some cases, inheritance has been described as likely de novo (Körkkö J et al. J Med Genet. 2002;39:34-41; Katzke S et al. Hum Mutat. 2002;20:197-208). Additionally, this alteration has been observed to co-segregate in multiple relatives in families with bilateral ectopia lentis (Yu R et al. Am J Ophthalmol. 2006;141(6):1136-8). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Dec 22, 2024