ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.298+1G>A (rs68058881)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000560147 SCV000631858 pathogenic Ornithine carbamoyltransferase deficiency 2017-06-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the OTC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with ornithine transcarbamylase deficiency (PMID: 8530002). ClinVar contains an entry for this variant (Variation ID: 97159). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in OTC are known to be pathogenic (PMID: 10946359). Two different variants affecting this nucleotide (c.298+1G>C, c.298+1G>T) have been determined to be pathogenic (PMID: 16786505, 25433810). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
GenMed Metabolism Lab RCV000083392 SCV000115478 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.

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