Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000197418 | SCV000250253 | uncertain significance | not provided | 2022-05-31 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Does not occur within a calcium-binding-EGF-like domain, and not located within exons 24-33, where the majority of pathogenic variants reported to date occur (Callewaert et al., 2008, Frederic et al., 2009); This variant is associated with the following publications: (PMID: 26582918, 27535533) |
Invitae | RCV001062854 | SCV001227677 | uncertain significance | Congenital contractural arachnodactyly | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2736 of the FBN2 protein (p.Gly2736Glu). This variant is present in population databases (rs149180427, gnomAD 0.006%). This missense change has been observed in individuals with aortic root dilatation and/or clinical features of congenital contractural arachnodactyly (Invitae). ClinVar contains an entry for this variant (Variation ID: 213369). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |