ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.3725G>A (p.Cys1242Tyr)

dbSNP: rs137854471
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000812017 SCV000952315 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2019-10-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant affects a cysteine residue in the EGF-like, TGFBP or hybrid motif domains of FBN1. Cysteine residues are believed to be involved in intramolecular disulfide bridges and have been shown to be important for FBN1 protein structure (PMID: 16905551, 19349279). In addition, missense substitutions affecting cysteine residues within these domains are significantly overrepresented among patients with Marfan syndrome (PMID: 16571647, 17701892). This variant has been reported to affect FBN1 protein function (PMID: 27893734). This variant has been observed to be de novo in individuals affected with Marfan syndrome (PMID: 8136837, 10486319) and has been observed in additional individuals affected with Marfan syndrome (PMID: 9401003, 19002209, 27906200). This variant is also known as C344Y in the literature. ClinVar contains an entry for this variant (Variation ID: 16429). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 1242 of the FBN1 protein (p.Cys1242Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine.
Centre of Medical Genetics, University of Antwerp RCV000017891 SCV002025286 pathogenic Marfan syndrome 2021-03-01 criteria provided, single submitter research PM2, PVS2, PP4
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital RCV000017891 SCV003935299 pathogenic Marfan syndrome criteria provided, single submitter clinical testing The heterozygous variant c.3725G>A (p.Cys1242Tyr) has been identified in a proband with severe myopia, marfanoid habits, hindfoot deformity, long slender fingers, chest deformity, mitral valve prolapsed and increased arm span. This variant is present in a mutation hotspot region where 4 pathogenic variants (PM1_moderate) have been reported and 1444 missense pathogenic variants in FBN1 gene have been reported (PP2_supporting). This variant is not found in gnomAD (Aggregated) (PM2_Moderate). This has been previously reported PMID: 19002209 (PP5_very strong).
OMIM RCV000017891 SCV000038170 pathogenic Marfan syndrome 1994-01-01 no assertion criteria provided literature only
Center for Medical Genetics Ghent, University of Ghent RCV000017891 SCV000786991 likely pathogenic 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.