U.S. flag

An official website of the United States government

NM_000138.5(FBN1):c.700G>T (p.Gly234Cys) AND Familial aortopathy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 3, 2024
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:
RCV004783115.1

Allele description [Variation Report for NM_000138.5(FBN1):c.700G>T (p.Gly234Cys)]

NM_000138.5(FBN1):c.700G>T (p.Gly234Cys)

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.700G>T (p.Gly234Cys)
HGVS:
  • NC_000015.10:g.48537647C>A
  • NG_008805.2:g.113142G>T
  • NM_000138.5:c.700G>TMANE SELECT
  • NM_001406716.1:c.700G>T
  • NM_001406717.1:c.700G>T
  • NP_000129.3:p.Gly234Cys
  • NP_000129.3:p.Gly234Cys
  • NP_001393645.1:p.Gly234Cys
  • NP_001393646.1:p.Gly234Cys
  • LRG_778t1:c.700G>T
  • LRG_778:g.113142G>T
  • LRG_778p1:p.Gly234Cys
  • NC_000015.9:g.48829844C>A
  • NM_000138.4:c.700G>T
Protein change:
G234C
Molecular consequence:
  • NM_000138.5:c.700G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406716.1:c.700G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406717.1:c.700G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial aortopathy
Identifiers:
MedGen: CN078214

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV005394133Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely pathogenic
(Sep 3, 2024)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005394133.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: FBN1 c.700G>T (p.Gly234Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The sulfhydryl group of cysteine is unique in its ability to participate in disulfide covalent cross-linkage. In fact, two-thirds of fibrillin cysteine residues exist in the half-cystinyl form, suggesting their participation in intramolecular disulfide linkage (PMID: 1301946). Therefore, this substitution resulting in the creation of a novel cysteine residue may disrupt the structure of the FBN1 protein, affecting its function. The variant was absent in 251282 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.700G>T in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2951150). Additionally, a different missense variant affecting the same codon, c.701G>T (p.G234V), has been reported in association with Marfan syndrome and aortic dissection in the literature and was also found to segregate with disease (PMIDs: 25370960, 28973303) Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Nov 18, 2024