Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000199525 | SCV000250160 | uncertain significance | not provided | 2022-08-12 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Although located in a calcium-binding EGF-like domain of the FBN2 gene, it does not substitute or introduce a cysteine residue (Callewaert et al., 2009; Frederic et al., 2009); This variant is associated with the following publications: (PMID: 19006240, 18767143) |
| Invitae | RCV000633601 | SCV000754847 | uncertain significance | Congenital contractural arachnodactyly | 2023-09-09 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 213278). This missense change has been observed in individuals with clinical features of congenital contractural arachnodactyly and/or thoracic aortic aneurysm (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 605 of the FBN2 protein (p.Gly605Ser). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN2 protein function. 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. |
| Ambry Genetics | RCV002408865 | SCV002711436 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-01-08 | criteria provided, single submitter | clinical testing | The p.G605S variant (also known as c.1813G>A), located in coding exon 13 of the FBN2 gene, results from a G to A substitution at nucleotide position 1813. The glycine at codon 605 is replaced by serine, an amino acid with similar properties, and is located in the cbEGF-like #05 domain. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |