ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.198C>A (p.Tyr66Ter)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287084 SCV001473728 likely pathogenic none provided 2019-11-19 criteria provided, single submitter clinical testing The FBN1 c.198C>A; p.Tyr66Ter variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, several downstream truncating variants have been described in individuals with Marfan syndrome and are considered pathogenic (Becerra-Munoz 2018, Rommel 2005). However, as the p.Tyr66Ter variant is located at the beginning of the transcript, use of a downstream start codon cannot be ruled out. Based on available information, this variant is considered to be likely pathogenic. References: Becerra-Munoz VM et al. The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome. Orphanet J Rare Dis. 2018 Jan 22;13(1):16. Rommel K et al. Identification of 29 novel and nine recurrent fibrillin-1 (FBN1) mutations and genotype-phenotype correlations in 76 patients with Marfan syndrome. Hum Mutat. 2005 Dec;26(6):529-39.

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.