Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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 | 2017-10-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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). 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. 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). This variant is not present in population databases (ExAC no frequency). 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. |
Genome- |
RCV000634848 | SCV002033226 | pathogenic | Ornithine carbamoyltransferase deficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Gen |
RCV000083528 | SCV000115614 | pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission to Pathogenic. |