Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000433496 | SCV000535494 | uncertain significance | not provided | 2017-01-09 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the COL5A2 gene. The P410S variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. This variant was not observed in the Exome Aggregation Consortium or 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 P410S 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 that is conserved in mammals. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, the P410S 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). However, in contrast to several other collagen genes, relatively few pathogenic Glycine substitutions have been reported in COL5A2 in association with EDS. Most pathogenic variants in COL5A2 are in-frame splice site changes that cause exon skipping (Symoens et al., 2012). |
Invitae | RCV002230294 | SCV000822644 | likely benign | Ehlers-Danlos syndrome, classic type, 1 | 2022-07-05 | criteria provided, single submitter | clinical testing |