Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000417646 | SCV000529699 | uncertain significance | not provided | 2016-07-07 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the FBN2 gene. The M1108L variant has not been publishedas a pathogenic variant or been reported as a benign variant to our knowledge. M1108L was not observed with anysignificant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBIExome Sequencing Project. Nevertheless, the M1108L variant is a conservative amino acid substitution, which is notlikely to impact secondary protein structure as these residues share similar properties. Additionally, this substitutionoccurs at a position where amino acids with properties similar to Methionine are tolerated across species, and L1108is tolerated in at least three species. Consequently, in silico analysis predicts this variant likely does not alter theprotein structure/function. Finally, while the M1108L variant is located within a calcium-binding EGF-like domain ofthe FBN2 gene, it does not affect a Cysteine residue. Cysteine substitutions in the calcium-binding EGF-likedomains represent the majority of pathogenic missense changes associated with congenital arachnodactyly (Collod-Beroud et al., 2003; Frédéric et al., 2009).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. |
| Labcorp Genetics |
RCV001341315 | SCV001535182 | benign | Congenital contractural arachnodactyly | 2024-12-20 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002480312 | SCV002784595 | uncertain significance | Congenital contractural arachnodactyly; Macular degeneration, early-onset | 2021-10-08 | criteria provided, single submitter | clinical testing |