Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000468929 | SCV000553186 | uncertain significance | Congenital contractural arachnodactyly | 2023-06-15 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 413 of the FBN2 protein (p.Tyr413Cys). 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. ClinVar contains an entry for this variant (Variation ID: 411820). This variant has not been reported in the literature in individuals affected with FBN2-related conditions. This variant is present in population databases (rs576123258, gnomAD 0.01%). |
Gene |
RCV001574507 | SCV001801341 | uncertain significance | not provided | 2019-10-14 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Although it introduces a cysteine residue, it does not occur 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 (Frederic et al., 2009); Reported as a variant of uncertain significance in ClinVar (SCV000553186.2; Landrum et al., 2016) |
Ce |
RCV001574507 | SCV003916980 | uncertain significance | not provided | 2023-03-01 | criteria provided, single submitter | clinical testing |