Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Johns Hopkins Genomics, |
RCV001007586 | SCV001167232 | uncertain significance | Osteogenesis imperfecta type I | 2019-10-18 | criteria provided, single submitter | clinical testing | This COL1A1 variant is absent from a large population dataset and has not been reported in ClinVar nor the literature, to our knowledge. This variant is located within major ligand binding region (MLBR) 2, which includes sites that are important for collagen self-assembly, cleavage, and binding. While glycine substitutions located within an MLBR are commonly reported as damaging, the effect of a proline substitution within one of these regions is unclear. Of three bioinformatics tools queried, two predict that the substitution would be damaging, while the third predicts that it would be tolerated. The proline residue at this position is evolutionarily conserved across all species assessed. Due to insufficient evidence, we consider the clinical significance of c.2215C>G to be uncertain at this time. |