ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.663+1G>T (rs68170503)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GenMed Metabolism Lab RCV000083528 SCV000115614 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.
GeneDx RCV000083528 SCV000516805 pathogenic not provided 2015-05-06 criteria provided, single submitter clinical testing The c.663+1 G>T splice site variant in the OTC gene has been previously reported in association with ornithine transcarbamylase (Oppliger Leibundgut et al., 1996). This variant destroys the canonical splice donor site in intron 6, and is expected to cause abnormal gene splicing. Therefore, we interpret this variant as pathogenic.
Invitae RCV000634848 SCV000756197 pathogenic Ornithine carbamoyltransferase deficiency 2017-11-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 6 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 to be de novo in an individual affected with ornithine transcarbamylase (OTC) deficiency (PMID: 8566955). ClinVar contains an entry for this variant (Variation ID: 97284). 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, 16786505). For these reasons, this variant has been classified as Pathogenic.

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