ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.988A>G (p.Arg330Gly) (rs72558478)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GenMed Metabolism Lab RCV000083625 SCV000115711 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.
GeneDx RCV000083625 SCV000582814 likely pathogenic not provided 2015-11-16 criteria provided, single submitter clinical testing The R330G variant has been published previously as a pathogenic variant in patients with ornithine transcarbamylase (OTC) deficiency (Tuchman et al. 1997; McCullough et al. 2000; Nagasaka et al. 2013). The R330G variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R330G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (E326K, W332R, M335I) have been reported in the Human Gene Mutation Database in association with OTC deficiency (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret the R330C variant to be likely pathogenic; however, the possibility that it is benign cannot be excluded.

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