ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.6187G>A (p.Ala2063Thr)

gnomAD frequency: 0.00001  dbSNP: rs1316593215
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
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506354 SCV000603644 uncertain significance not specified 2017-01-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV001178175 SCV000738751 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-12-20 criteria provided, single submitter clinical testing The p.A2063T variant (also known as c.6187G>A), located in coding exon 50 of the FBN1 gene, results from a G to A substitution at nucleotide position 6187. The alanine at codon 2063 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and threonine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001046063 SCV001209948 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-03-09 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001178175 SCV001342551 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-10-25 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 2063 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 1/251142 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 RCV001591155 SCV001815083 uncertain significance not provided 2019-04-19 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance by other clinical laboratories (ClinVar Variant ID# 439707; Landrum et al., 2016)
Fulgent Genetics, Fulgent Genetics RCV002481637 SCV002789986 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 2021-08-27 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004003557 SCV004822455 uncertain significance Marfan syndrome 2023-11-20 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the TGFbeta-like domain 8 of the FBN1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/245894 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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.