Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317066 | SCV001983728 | pathogenic | Hyperornithinemia | 2023-06-07 | criteria provided, single submitter | clinical testing | Variant summary: OAT c.1307T>A (p.Ile436Asn) 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 allele was found at a frequency of 1.2e-05 in 249942 control chromosomes. c.1307T>A has been reported in the literature in at least two individuals affected with Gyrate Atrophy Of Choroid And Retina (Doimo_2012, Casalino_2018). These data indicate that the variant is likely to 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 (Doimo_2012). The following publications have been ascertained in the context of this evaluation (PMID: 29654911, 23076989). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV000049524 | SCV004295740 | pathogenic | Ornithine aminotransferase deficiency | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 436 of the OAT protein (p.Ile436Asn). This variant is present in population databases (rs386833598, gnomAD 0.003%). This missense change has been observed in individual(s) with gyrate atrophy of choroid and retina (PMID: 23076989, 29654911). ClinVar contains an entry for this variant (Variation ID: 56115). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects OAT function (PMID: 23076989). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000049524 | SCV005053764 | likely pathogenic | Ornithine aminotransferase deficiency | 2024-02-27 | criteria provided, single submitter | clinical testing | |
| Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000049524 | SCV000081961 | probable-pathogenic | Ornithine aminotransferase deficiency | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |