Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000990789 | SCV001141826 | pathogenic | Ornithine carbamoyltransferase deficiency | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000990789 | SCV005842260 | likely pathogenic | Ornithine carbamoyltransferase deficiency | 2024-10-21 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 169 of the OTC protein (p.Pro169Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with OTC deficiency (PMID: 11117428, 34014569). ClinVar contains an entry for this variant (Variation ID: 97228). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt OTC protein function with a positive predictive value of 95%. This variant disrupts the p.Pro169 amino acid residue in OTC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11793468). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
Gen |
RCV000083468 | SCV000115554 | pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission to Pathogenic. |