ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.32T>G (p.Leu11Arg)

dbSNP: rs1555407429
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
Centre of Medical Genetics, University of Antwerp RCV000663627 SCV002025388 likely pathogenic Marfan syndrome 2021-03-01 criteria provided, single submitter research PM2, PS1, PP4
Invitae RCV001855413 SCV002134833 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-03-10 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Leu11 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been observed in individuals with FBN1-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN1 protein function. ClinVar contains an entry for this variant (Variation ID: 549153). This missense change has been observed in individuals with clinical features of Marfan syndrome (PMID: 21542060, 29907982; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 11 of the FBN1 protein (p.Leu11Arg).
Center for Medical Genetics Ghent, University of Ghent RCV000663627 SCV000786949 uncertain significance Marfan syndrome 2017-11-07 no assertion criteria provided 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.