ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.669G>A (p.Met223Ile)

dbSNP: rs910928261
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
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 RCV000780234 SCV000917342 uncertain significance not specified 2018-05-14 criteria provided, single submitter clinical testing Variant summary: FBN1 c.669G>A (p.Met223Ile) results in a conservative amino acid change located in a TB domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 246152 control chromosomes (gnomAD). 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.669G>A in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000810633 SCV000950854 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-07-13 criteria provided, single submitter clinical testing
Wangler Lab, Baylor College of Medicine RCV002287445 SCV002577613 uncertain significance Marfan syndrome criteria provided, single submitter clinical testing This FBN1 missense variant at c.669G>A (p.M223I) was discovered on exome through the Texome Project (R01HG011795). It was observed in gnomAD with a frequency of <0.001%. It has an inconclusive CADD score (22.900) and the evolutionary conservation of this residue is high. This variant is located in one of the TGF-β-binding protein-like domains of the fibrillin protein, and variants in nearby residues have been described in individuals with Marfan syndrome (PM1). We classify this as a variant of uncertain significant.
Baylor Genetics RCV002287445 SCV003836319 uncertain significance Marfan syndrome 2022-04-20 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.