Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV000208361 | SCV000263927 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2015-04-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001338220 | SCV001531872 | uncertain significance | Congenital contractural arachnodactyly | 2020-09-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with FBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 222627). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 1054 of the FBN2 protein (p.Arg1054Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. 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. |