ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.3412T>C (p.Cys1138Arg) (rs1131691806)

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
GeneDx RCV000493457 SCV000582882 pathogenic not provided 2018-05-17 criteria provided, single submitter clinical testing The C1138R variant in the FBN1 gene has been reported as occuring de novo in an individual with classic Marfan syndrome (Stheneur et al., 2009). Additionally, the C1138R variant has been identified independently of other cardiogenetic variants in one individual referred for TAAD/Marfan syndrome genetic testing at GeneDx. This variant is not observed in large population cohorts (Lek et al., 2016). The C1138R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, {support a deleterious effect. Furthermore, missense variants in the same residue (C1138G, C1138S, C1138Y) and in nearby residues (R1137P, C1140F) have been reported in the Human Gene Mutation Database in association with FBN1-related disorders (Stenson et al., 2014). Finally, the C1138R variant affects a Cysteine residue within the 17th calcium-binding EGF-like domain of the FBN1 gene, which participates in disulfide bonding with the C1124 residue and is predicted to alter the structure and function of the protein. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with Marfan syndrome (Collod-Beroud et al., 2003).
Center for Medical Genetics Ghent,University of Ghent RCV000663638 SCV000786961 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.