ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.8177G>A (p.Arg2726Gln)

gnomAD frequency: 0.00001  dbSNP: rs552157433
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000226999 SCV000283656 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-03-22 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001189718 SCV001357068 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-15 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 2726 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with FBN1-related disorders in the literature. This variant has been identified in 11/251462 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV002286724 SCV002576960 uncertain significance not provided 2022-09-27 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Does not affect a cysteine residue within a calcium-binding EGF-like domain or a TGF-binding protein domain of the FBN1 gene; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disorders (Collod-Beroud et al., 2003); This variant is associated with the following publications: (PMID: 12938084)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003235151 SCV003934309 uncertain significance not specified 2023-05-15 criteria provided, single submitter clinical testing Variant summary: FBN1 c.8177G>A (p.Arg2726Gln) results in a conservative amino acid change in 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 4.4e-05 in 251462 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in FBN1 causing Marfan Syndrome (4.4e-05 vs 0.00011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.8177G>A in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified it as VUS (n=3) or likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
All of Us Research Program, National Institutes of Health RCV000664015 SCV004844920 uncertain significance Marfan syndrome 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 2726 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 11/251462 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Center for Medical Genetics Ghent, University of Ghent RCV000664015 SCV000787403 uncertain significance 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.