Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Medical Genetics and Applied Genomics, |
RCV001291597 | SCV001480146 | likely pathogenic | not provided | 2021-02-01 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001329809 | SCV001521346 | likely pathogenic | Camptomelic dysplasia | criteria provided, single submitter | clinical testing | ||
| Institute of Human Genetics, |
RCV001329809 | SCV001739384 | pathogenic | Camptomelic dysplasia | 2021-04-21 | criteria provided, single submitter | clinical testing | The variant was not found in DNA extracted from the parents' blood samples (PS2), the variant is absent from controls (gnomAD; PM2), multiple lines of computational evidence support a deleterious effect (PP3) and it is localized at an amino acid site where different missense changes determined to be pathogenic have been seen before (PM5); therefore we classified it as pathogenic according to ACMG criteria. |
| Labcorp Genetics |
RCV001329809 | SCV002259073 | likely pathogenic | Camptomelic dysplasia | 2022-06-20 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 170 of the SOX9 protein (p.Pro170Ala). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Pro170 amino acid residue in SOX9. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9002675). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SOX9 protein function. ClinVar contains an entry for this variant (Variation ID: 996802). This variant has not been reported in the literature in individuals affected with SOX9-related conditions. This variant is not present in population databases (gnomAD no frequency). |