ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.814_816GAG[1] (p.Glu273del) (rs72558452)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000692945 SCV000820796 uncertain significance Ornithine carbamoyltransferase deficiency 2018-04-20 criteria provided, single submitter clinical testing This variant, c.817_819delGAG, results in the deletion of 1 amino acid of the OTC protein (p.Glu273del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a male individual affected with late onset hyperammonemic coma whose liver OTC activity averaged 5% of control  (PMID: 8956045). ClinVar contains an entry for this variant (Variation ID: 97337). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. 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.
Integrated Genetics/Laboratory Corporation of America RCV000692945 SCV001360757 likely pathogenic Ornithine carbamoyltransferase deficiency 2019-11-01 criteria provided, single submitter clinical testing Variant summary: OTC c.817_819delGAG (p.Glu273del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 5.5e-06 in 183136 control chromosomes (gnomAD). c.817_819delGAG has been reported in the literature in individuals affected with late-onset Ornithine Transcarbamylase Deficiency (Segues_1996, Arranz_2007, Martin-Hernandez_2014). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.
GenMed Metabolism Lab RCV000083584 SCV000115670 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.

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