ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.1573C>T (p.Arg525Trp)

dbSNP: rs768253008
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000552580 SCV000627841 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-12-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 525 of the FBN1 protein (p.Arg525Trp). This variant is present in population databases (rs768253008, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 457164). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt FBN1 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health RCV001186601 SCV001353068 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-10-25 criteria provided, single submitter clinical testing This missense variant replaces arginine with tryptophan at codon 525 of the FBN1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual who was affected with ischemic stroke (PMID: 36973604). This variant has been identified in 5/251290 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.
AiLife Diagnostics, AiLife Diagnostics RCV002223860 SCV002503243 uncertain significance not provided 2021-12-30 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002506298 SCV002815565 uncertain significance Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome 2021-10-05 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV002223860 SCV004227414 uncertain significance not provided 2022-09-20 criteria provided, single submitter clinical testing BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV002223860 SCV004564536 uncertain significance not provided 2023-10-19 criteria provided, single submitter clinical testing The FBN1 c.1573C>T; p.Arg525Trp variant (rs768253008), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 457164). This variant is found in the Latino/Admixed American population with an allele frequency of 0.015% (5/34,564 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is deleterious (REVEL: 0.731). However, given the lack of clinical and functional data, the significance of this variant is uncertain at this time.
All of Us Research Program, National Institutes of Health RCV004003779 SCV004823044 uncertain significance Marfan syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces arginine with tryptophan at codon 525 of the FBN1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 5/251290 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.
Breakthrough Genomics, Breakthrough Genomics RCV002223860 SCV005193793 uncertain significance not provided criteria provided, single submitter not provided

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.