Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001246067 | SCV001419400 | uncertain significance | Congenital hyperammonemia, type I | 2021-07-14 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with leucine at codon 1203 of the CPS1 protein (p.Ser1203Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs149518280, ExAC 0.001%). This missense change has been observed in individual(s) with CPS1 deficiency (PMID: 21120950; Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Ser1203 amino acid residue in CPS1. Other variant(s) that disrupt this residue have been observed in individuals with CPS1-related conditions (PMID: 9686343, 16737834), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Al Jalila Children's Genomics Center, |
RCV002508796 | SCV002818142 | likely pathogenic | not provided | 2022-12-17 | criteria provided, single submitter | clinical testing |