ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.7072G>A (p.Val2358Ile)

gnomAD frequency: 0.00028  dbSNP: rs140537304
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000757279 SCV000233892 likely benign not provided 2021-04-28 criteria provided, single submitter clinical testing Has been previously reported in published literature (Groth et al., 2017); 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 (ClinVar Variant ID# 36111; Landrum et al., 2016); Observed in 55/282,216 (0.02%) alleles in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27906200)
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 2023-10-23 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 benign Marfan syndrome 2023-08-22 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001183241 SCV001348922 likely benign Familial thoracic aortic aneurysm and aortic dissection 2020-02-11 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001183241 SCV003838341 likely benign Familial thoracic aortic aneurysm and aortic dissection 2022-02-28 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.