Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000674758 | SCV000800150 | likely pathogenic | Congenital hyperammonemia, type I | 2018-05-23 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000674758 | SCV003485152 | pathogenic | Congenital hyperammonemia, type I | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 810 of the CPS1 protein (p.Gln810Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with carbamoyl phosphate synthetase I deficiency (PMID: 12955727, 16737834, 22173106). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.2552A>G. ClinVar contains an entry for this variant (Variation ID: 558483). 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 CPS1 protein function with a positive predictive value of 80%. This variant disrupts the p.Gln810 amino acid residue in CPS1. Other variant(s) that disrupt this residue have been observed in individuals with CPS1-related conditions (PMID: 33611823), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |