ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.8081G>A (p.Arg2694Gln)

dbSNP: rs371375126
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 RCV001040428 SCV001204003 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-12-19 criteria provided, single submitter clinical testing
GeneDx RCV001582618 SCV001813150 uncertain significance not provided 2021-06-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Does not affect a cysteine residue within a calcium-binding EGF-like 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).; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 161240; Landrum et al., 2016); Has been identified in one individual with the clinical suspicion of Marfan syndrome in published literature (Hung et al., 2009); This variant is associated with the following publications: (PMID: 19839986, 24833718, 26582918, 12938084, 25637381, 25812041, 24941995)
Color Diagnostics, LLC DBA Color Health RCV001804856 SCV002052677 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-02-13 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 2694 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 been reported in an individual with suspected Marfan Syndrome (PMID: 19839986). This variant has been identified in 1/251390 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.
All of Us Research Program, National Institutes of Health RCV000148495 SCV004844925 uncertain significance Marfan syndrome 2024-09-23 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 2694 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 been reported in an individual with suspected Marfan Syndrome (PMID: 19839986). This variant has been identified in 1/251390 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.
Ambry Genetics RCV001804856 SCV005585738 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-08-26 criteria provided, single submitter clinical testing The p.R2694Q variant (also known as c.8081G>A), located in coding exon 64 of the FBN1 gene, results from a G to A substitution at nucleotide position 8081. The arginine at codon 2694 is replaced by glutamine, an amino acid with highly similar properties. This variant has been reported cohorts with suspected Marfan syndrome, but clinical details were limited (Hung CC et al. Ann Hum Genet, 2009 Nov;73:559-67; Han D et al. Mol Genet Genomic Med, 2024 Jul;12:e2482). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
CSER _CC_NCGL, University of Washington RCV000148495 SCV000190202 uncertain significance Marfan syndrome 2014-06-01 no assertion criteria provided research

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.