ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.386G>A (p.Arg129His) (rs66656800)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000011757 SCV001224329 pathogenic Ornithine carbamoyltransferase deficiency 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 129 of the OTC protein (p.Arg129His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant also falls at the last nucleotide of exon 4 of the OTC coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with ornithine transcarbamylase (OTC) deficiency (PMID: 8081398, 29581464, 30285816, 7860064, 25853564, 8807340, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 11010). 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"). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 25853564). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000011757 SCV000031989 pathogenic Ornithine carbamoyltransferase deficiency 1995-02-01 no assertion criteria provided literature only
GenMed Metabolism Lab RCV000083414 SCV000115500 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.

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