Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000444112 | SCV000536620 | uncertain significance | not provided | 2017-01-31 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the FBN2 gene. The R1989C variant has not been published as pathogenic or been reported as benign to our knowledge. The R1989C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1989C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, the R1989C variant affects a Cysteine residue within a calcium-binding EGF-like domain of the FBN2 gene, which may affect disulfide bonding and is predicted to alter the structure and function of the protein. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with CCA (Collod-Beroud et al., 2003; Frédéric et al, 2009). Nevertheless, this substitution occurs at a position that is not conserved across species. |
Invitae | RCV003640899 | SCV004537899 | likely benign | Congenital contractural arachnodactyly | 2022-11-14 | criteria provided, single submitter | clinical testing |