Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000792966 | SCV000932297 | likely pathogenic | Ornithine carbamoyltransferase deficiency | 2020-06-10 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 53 of the OTC protein (p.Ile53Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with ornithine transcarbamylase deficiency (PMID: 16786505, Invitae, external communication). ClinVar contains an entry for this variant (Variation ID: 97122). 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Ile53 amino acid residue in OTC. Other variant(s) that disrupt this residue have been observed in individuals with OTC-related conditions (PMID: 11793468), which suggests that this may be a clinically significant amino acid residue. 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. |
Gen |
RCV000083351 | SCV000115437 | pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission to Pathogenic. |