Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000000175 | SCV001485997 | uncertain significance | Ornithine aminotransferase deficiency | 2022-11-22 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects OAT function (PMID: 1737786, 34395527). 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. 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 OAT protein function. ClinVar contains an entry for this variant (Variation ID: 152). This missense change has been observed in individual(s) with gyrate atrophy of the choroid and retina (PMID: 1737786). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 154 of the OAT protein (p.Arg154Leu). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001824555 | SCV002074387 | likely pathogenic | Hyperornithinemia | 2024-08-06 | criteria provided, single submitter | clinical testing | Variant summary: OAT c.461G>T (p.Arg154Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251370 control chromosomes. c.461G>T has been reported in the literature in one homozygous individual affected with Ornithine Aminotransferase Deficiency (Brody_1992). These data indicate that the variant may be associated with disease. Functionally, the variant was found to inhibit normal enzymatic activity in both cell culture and in vitro assays. Fibroblasts from a homozygous patient and transfected CHO cells had no observable enzymatic activity (Brody_1992). This was further investigated by using purified proteins produced in E. coli, where the variant protein was shown to have deficits in forming functional tetramers, instead forming non-functional dimers (Montioli_2021). The variant also had 350-fold lower catalytic activity in vitro (Montioli_2021). The following publications have been ascertained in the context of this evaluation (PMID: 1737786, 34395527). ClinVar contains an entry for this variant (Variation ID: 152). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000000175 | SCV004208951 | likely pathogenic | Ornithine aminotransferase deficiency | 2023-12-13 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000000175 | SCV000020318 | pathogenic | Ornithine aminotransferase deficiency | 1992-02-15 | no assertion criteria provided | literature only |