ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.803T>C (p.Met268Thr) (rs72558449)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000702113 SCV000830948 pathogenic Ornithine carbamoyltransferase deficiency 2018-03-14 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 268 of the OTC protein (p.Met268Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with ornithine transcarbamylase deficiency (PMID: 8365726, 12083811, 9286441). ClinVar contains an entry for this variant (Variation ID: 97333). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. A different nucleotide substitution (c.802A>G) at this codon (p.Met268Thr) has been reported in an individual affected with ornithine transcarbamylase deficiency (PMID: 23821427). For these reasons, this variant has been classified as Pathogenic.
GenMed Metabolism Lab RCV000083580 SCV000115666 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.

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