Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001189727 | SCV000738904 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-06-05 | criteria provided, single submitter | clinical testing | The p.I547V variant (also known as c.1639A>G), located in coding exon 13 of the FBN1 gene, results from an A to G substitution at nucleotide position 1639. The isoleucine at codon 547 is replaced by valine, an amino acid with highly similar properties, and is located in the cbEGF-like #4 domain. This amino acid position is not well conserved in available vertebrate species, and valine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV001189727 | SCV001357079 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-01-18 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 547 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 2/251276 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. |
| Labcorp Genetics |
RCV001320564 | SCV001511355 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-08-31 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004002728 | SCV004823037 | uncertain significance | Marfan syndrome | 2023-08-14 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 547 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 2/251276 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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. |
| Fulgent Genetics, |
RCV005004271 | SCV005633073 | 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 | 2024-05-13 | criteria provided, single submitter | clinical testing |