Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000198329 | SCV000250191 | uncertain significance | not provided | 2016-10-03 | criteria provided, single submitter | clinical testing | The S1148G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S1148G 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, this substitution occurs at a position where only amino acids with similar properties to Serine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, while the S1148G variant is located within a calcium-binding EGF-like domain of the FBN2 gene, it does not affect a Cysteine residue within this domain. 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). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
| Ambry Genetics | RCV001265725 | SCV001443894 | uncertain significance | Inborn genetic diseases | 2017-12-11 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001318629 | SCV001509341 | benign | Congenital contractural arachnodactyly | 2023-08-08 | criteria provided, single submitter | clinical testing |