ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.5330G>A (p.Cys1777Tyr) (rs1060501069)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585388 SCV000692813 likely pathogenic not provided 2017-10-31 criteria provided, single submitter clinical testing
Center for Medical Genetics Ghent,University of Ghent RCV000467273 SCV000787126 pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing
Invitae RCV000467273 SCV000544911 likely pathogenic Marfan syndrome 2016-10-31 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 1777 of the FBN1 protein (p.Cys1777Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FBN1-related disease. This variant affects a cysteine residue located within an epidermal-growth-factor (EGF)-like 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: 10486319, 3495735, 4750422, 16677079). In addition, missense substitutions within the FBN1 EGF-like domains affecting cysteine residues are significantly overrepresented among patients with Marfan syndrome (PMID: 16571647, 17701892). In summary, this variant is a novel missense change affecting a residue crucial for protein stability and function. Although additional genetic data will be necessary to further confirm pathogenicity for this variant, cysteine substitutions located in FBN1 EGF-like domains are likely deleterious. For these reasons, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.