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NM_000138.5(FBN1):c.1982G>A (p.Cys661Tyr) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 18, 2016
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:
RCV001381625.7

Allele description [Variation Report for NM_000138.5(FBN1):c.1982G>A (p.Cys661Tyr)]

NM_000138.5(FBN1):c.1982G>A (p.Cys661Tyr)

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.1982G>A (p.Cys661Tyr)
HGVS:
  • NC_000015.10:g.48503918C>T
  • NG_008805.2:g.146871G>A
  • NM_000138.5:c.1982G>AMANE SELECT
  • NP_000129.3:p.Cys661Tyr
  • NP_000129.3:p.Cys661Tyr
  • LRG_778t1:c.1982G>A
  • LRG_778:g.146871G>A
  • LRG_778p1:p.Cys661Tyr
  • NC_000015.9:g.48796115C>T
  • NM_000138.4:c.1982G>A
Protein change:
C661Y
Links:
dbSNP: rs1060501086
NCBI 1000 Genomes Browser:
rs1060501086
Molecular consequence:
  • NM_000138.5:c.1982G>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
SCV001580103Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 18, 2016) 		germlineclinical testing

PubMed (8)
[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

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

Genotype impacts survival in Marfan syndrome.

Franken R, Groenink M, de Waard V, Feenstra HM, Scholte AJ, van den Berg MP, Pals G, Zwinderman AH, Timmermans J, Mulder BJ.

Eur Heart J. 2016 Nov 14;37(43):3285-3290. Epub 2016 Jan 18.

PubMed [citation]
PMID:
26787436
See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001580103.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This variant has been reported in individuals affected with Marfan syndrome (PMID: 12203992, 26787436). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 661 of the FBN1 protein (p.Cys661Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. For these reasons, this variant has been classified as Pathogenic. This variant affects a cysteine residue located within an TGFBP domain of the FBN1 protein. Cysteine residues in these domains have been shown to be involved in the formation of disulfide bridges, which are critical for FBN1 protein structure and stability (PMID: 11104663, 12203987, 16677079). In addition, missense substitutions within the TGFBP domains affecting cysteine residues are significantly overrepresented among patients with Marfan syndrome (PMID: 16571647, 17701892).

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

Last Updated: Sep 29, 2024