ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.7688C>T (p.Ser2563Phe)

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
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004766631 SCV005381527 uncertain significance not specified 2024-08-28 criteria provided, single submitter clinical testing Variant summary: FBN1 c.7688C>T (p.Ser2563Phe) results in a non-conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 249628 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.7688C>T in individuals affected with FBN1-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV005221053 SCV005864169 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-11-27 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 2563 of the FBN1 protein (p.Ser2563Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FBN1 protein function with a negative predictive value of 95%. 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.

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.