Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001295432 | SCV001484352 | likely pathogenic | Ornithine carbamoyltransferase deficiency | 2023-03-23 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with OTC-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 196 of the OTC protein (p.Asp196Glu). ClinVar contains an entry for this variant (Variation ID: 999435). 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.Asp196 amino acid residue in OTC. Other variant(s) that disrupt this residue have been observed in individuals with OTC-related conditions (PMID: 16786505, 21488237), which suggests that this may be a clinically significant amino acid residue. 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. |