ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.1238A>G (p.Tyr413Cys)

gnomAD frequency: 0.00002  dbSNP: rs576123258
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
Invitae RCV000468929 SCV000553186 uncertain significance Congenital contractural arachnodactyly 2023-06-15 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 413 of the FBN2 protein (p.Tyr413Cys). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 not expected to disrupt FBN2 protein function. ClinVar contains an entry for this variant (Variation ID: 411820). This variant has not been reported in the literature in individuals affected with FBN2-related conditions. This variant is present in population databases (rs576123258, gnomAD 0.01%).
GeneDx RCV001574507 SCV001801341 uncertain significance not provided 2019-10-14 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Although it introduces a cysteine residue, it does not occur within a calcium-binding EGF-like domain of the FBN2 gene; Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN2 related disorders (Frederic et al., 2009); Reported as a variant of uncertain significance in ClinVar (SCV000553186.2; Landrum et al., 2016)
CeGaT Center for Human Genetics Tuebingen RCV001574507 SCV003916980 uncertain significance not provided 2023-03-01 criteria provided, single submitter 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.