Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003079116 | SCV003460069 | likely pathogenic | Ornithine aminotransferase deficiency | 2023-10-09 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 158 of the OAT protein (p.Tyr158Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with gyrate atrophy (PMID: 29757052). ClinVar contains an entry for this variant (Variation ID: 2152099). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects OAT function (PMID: 36834788). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005406579 | SCV006071364 | likely pathogenic | Hyperornithinemia | 2025-03-25 | criteria provided, single submitter | clinical testing | Variant summary: OAT c.473A>C (p.Tyr158Ser) 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 251364 control chromosomes. c.473A>C has been reported in the homozygous state in the literature in at least 1 individual affected with Ornithine Aminotransferase Deficiency (example, Cui_2018, Liu_2025). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity in vitro (example, Floriani_2023). The following publications have been ascertained in the context of this evaluation (PMID: 29757052, 36834788, 39127396). ClinVar contains an entry for this variant (Variation ID: 2152099). Based on the evidence outlined above, the variant was classified as likely pathogenic. |