Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001379672 | SCV001577512 | likely pathogenic | Ornithine carbamoyltransferase deficiency | 2021-02-02 | criteria provided, single submitter | clinical testing | 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.Leu179 amino acid residue in OTC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17334707, 30285816, 22727265, 16786505). 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 OTC protein function. This variant has not been reported in the literature in individuals with OTC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 179 of the OTC protein (p.Leu179Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. |