ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.154G>A (p.Glu52Lys) (rs66521141)

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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 RCV000083347 SCV000115433 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.
Invitae RCV000807816 SCV000947890 pathogenic Ornithine carbamoyltransferase deficiency 2018-10-02 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 52 of the OTC protein (p.Glu52Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with ornithine transcarbamylase (OTC) deficiency (PMID: 10946359, 25433810, 17334707), being de novo in one of them (Invitae). ClinVar contains an entry for this variant (Variation ID: 97118). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). The observation of one or more missense substitutions at this codon (p.Glu52Lys and p.Glu52Asp) in affected individuals suggests that this may be a clinically significant residue (PMID: 10946359, 25433810, 17334707). For these reasons, this variant has been classified as Pathogenic.

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