ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.1468G>T (p.Asp490Tyr)

dbSNP: rs1555400371
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 RCV000663461 SCV002025477 pathogenic Marfan syndrome 2021-03-01 criteria provided, single submitter research PM2, PS6, PP4
Invitae RCV003767926 SCV004570974 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-01-06 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 490 of the FBN1 protein (p.Asp490Tyr). This variant also falls at the last nucleotide of exon 12, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of FBN1-related conditions (PMID: 11826022, 20886638, 35058154; Invitae). ClinVar contains an entry for this variant (Variation ID: 549019). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Center for Medical Genetics Ghent, University of Ghent RCV000663461 SCV000786755 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.