Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000486163 | SCV000571400 | uncertain significance | not provided | 2018-04-09 | criteria provided, single submitter | clinical testing | The variant of uncertain significance K262T in the COL5A2 gene has not been published as a pathogenic or 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 K262T variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties, and occurs at a position conserved across species. Consequently, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with EDS (Stenson et al., 2014), and the K262T variant does not affect a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL5A2 gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |