ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.2287T>C (p.Cys763Arg) (rs1555399361)

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
Ambry Genetics RCV000617292 SCV000738872 likely pathogenic Cardiovascular phenotype 2017-09-05 criteria provided, single submitter clinical testing The p.C763R variant (also known as c.2287T>C), located in coding exon 18 of the FBN1 gene, results from a T to C substitution at nucleotide position 2287. The cysteine at codon 763 is replaced by arginine, an amino acid with highly dissimilar properties, and is predicted to disrupt disulfide bonding in the cbEGF-like #07 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 amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781359 SCV000919335 uncertain significance not specified 2018-03-12 criteria provided, single submitter clinical testing Variant summary: FBN1 c.2287T>C (p.Cys763Arg) results in a non-conservative amino acid change located in the EGF-like domain of the encoded protein sequence. Cysteins are critical for FBN1 function. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 121392 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.2287T>C in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance-possibly pathogenic.
Invitae RCV001377643 SCV001575026 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2020-02-05 criteria provided, single submitter clinical testing

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.