ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.7072G>A (p.Val2358Ile) (rs140537304)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000757279 SCV000233892 uncertain significance not provided 2017-01-20 criteria provided, single submitter clinical testing The V2358I variant of uncertain significance in the FBN1 gene has not been published as pathogenic or benign to our knowledge. The NHLBI Exome Sequencing Project and Exome Aggregation Consortium report V2358I has been observed in 0.11% to 0.12% of alleles from individuals of African or African American background, indicating it may be a rare variant in this population. This substitution occurs at a position that is conserved across species, and the majority of in silico tools predict this variant is probably damaging to the protein structure/function. Nevertheless, the V2358I variant is a conservative amino acid substitution, which may not impact secondary protein structure as these residues share similar properties. Furthermore, V2358I 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).
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000029773 SCV000296875 uncertain significance Marfan syndrome 2015-10-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000181589 SCV000695591 benign not specified 2017-06-28 criteria provided, single submitter clinical testing Variant summary: The FBN1 c.7072G>A (p.Val2358Ile) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant. Multiple clinical diagnostic laboratories/reputable databases classified this variant as VUS. However, this variant was found in 30/121026 control chromosomes at a frequency of 0.0002479, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic FBN1 variant (0.0001125), suggesting this variant is likely a benign polymorphism. Supporting its benign nature, this variant has been found in one internal sample which carries a likely pathogenic FBN1 variant (c.1728C>A/p.Cys576X). Taken together, this variant is classified as benign.
Invitae RCV001087538 SCV000753148 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2020-09-14 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757279 SCV000885438 uncertain significance not provided 2017-10-18 criteria provided, single submitter clinical testing
Mendelics RCV000029773 SCV001139589 uncertain significance Marfan syndrome 2019-05-28 criteria provided, single submitter clinical testing
Color Health, Inc RCV001183241 SCV001348922 likely benign Familial thoracic aortic aneurysm and aortic dissection 2020-02-11 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.