Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000666361 | SCV000790640 | uncertain significance | Congenital hyperammonemia, type I | 2017-04-04 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001756125 | SCV001986016 | uncertain significance | not provided | 2020-01-29 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Identified in two individuals from a cohort of patients with CPS1 deficiency, however specific clinical information on patients was not provided, nor was the presence of a second variant in CPS1 discussed (Haberle et al., 2011); This variant is associated with the following publications: (PMID: 20800523, 21120950, 19092443, 19309799) |
Invitae | RCV000666361 | SCV004293069 | likely pathogenic | Congenital hyperammonemia, type I | 2023-04-06 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 551329). This missense change has been observed in individual(s) with CPS1-related conditions (PMID: 21120950, 33309754). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1089 of the CPS1 protein (p.Arg1089Cys). This variant disrupts the p.Arg1089 amino acid residue in CPS1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15876373, 16737834). 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. |