Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001043746 | SCV001207507 | uncertain significance | Congenital contractural arachnodactyly | 2023-09-03 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 841508). This variant has not been reported in the literature in individuals affected with FBN2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2715 of the FBN2 protein (p.Gly2715Arg). |
Genome Diagnostics Laboratory, |
RCV002276598 | SCV002566599 | uncertain significance | Connective tissue disorder | 2022-04-26 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002416359 | SCV002680326 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-01-29 | criteria provided, single submitter | clinical testing | The p.G2715R variant (also known as c.8143G>C), located in coding exon 63 of the FBN2 gene, results from a G to C substitution at nucleotide position 8143. The glycine at codon 2715 is replaced by arginine, an amino acid with dissimilar properties, and is located in the fibulin-like 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. |