Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489774 | SCV000576576 | uncertain significance | not provided | 2017-04-27 | criteria provided, single submitter | clinical testing | The N1529D variant has not beenpublished as pathogenic or been reported as benign to our knowledge. It is not observed in large population cohorts(Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The N1529D variant is asemi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ insome properties. Moreover, this substitution occurs at a position that is conserved across species, and in silicoanalysis predicts this variant is probably damaging to the protein structure/function. However, although this variantresides within the calcium-binding EGF-like domain of the FBN2 gene, it does not affect a cysteine residue. Cysteinesubstitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changesassociated with CCA (Collod-Beroud et al., 2003; Frédéric et al., 2009). |
| Invitae | RCV003640902 | SCV004403724 | uncertain significance | Congenital contractural arachnodactyly | 2023-05-20 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 426192). 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 asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 1529 of the FBN2 protein (p.Asn1529Asp). |