Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523705 | SCV000619098 | uncertain significance | not provided | 2020-12-04 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Does not affect a cysteine residue within a calcium-binding EGF-like domain of the FBN2 gene; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN2-related disorders (Collod-Beroud et al., 2003; Frederic et al., 2009). |
| Invitae | RCV001853641 | SCV002199297 | uncertain significance | Congenital contractural arachnodactyly | 2022-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2820 of the FBN2 protein (p.Glu2820Lys). This variant is present in population databases (rs752384882, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with FBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 450503). 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. 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. |