ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.2638G>C (p.Gly880Arg)

dbSNP: rs794728194
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001388388 SCV001589355 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2021-09-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change replaces glycine with arginine at codon 880 of the FBN1 protein (p.Gly880Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Marfan syndrome (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 406335). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant disrupts the p.Gly880 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12402346, 15821637, 18435798, 22772377). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.
GeneDx RCV004800414 SCV005421373 likely pathogenic not provided 2024-06-04 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign in association with an FBN1-related disorder to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Although located in a TGF-binding protein domain (aka TB domain or 8-Cysteine domain), it does not affect a cysteine residue within this domain; other missense substitutions that affect cysteine residues within this TGF-binding protein domain have been reported in association with various FBN1-related phenotypes (HGMD); This variant is associated with the following publications: (PMID: 27906200)

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.