Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
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 |
RCV001046063 | SCV001209948 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-03-09 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
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. |
Gene |
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, |
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, |
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. |