Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000196182 | SCV000250164 | uncertain significance | not provided | 2022-09-23 | 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 | RCV001853142 | SCV002124441 | uncertain significance | Congenital contractural arachnodactyly | 2023-09-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with FBN2-related conditions. This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 663 of the FBN2 protein (p.Gln663Pro). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 213282). 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 not expected to disrupt FBN2 protein function. |