Submissions for variant NM_000531.6(OTC):c.67C>T (p.Arg23Ter)

dbSNP: rs72552300

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001802797	SCV000884272	pathogenic	Ornithine carbamoyltransferase deficiency	2021-07-01	criteria provided, single submitter	clinical testing	The OTC c.67C>T; p.Arg23Ter variant (rs72552300) is reported in the literature in individuals affected with ornithine transcarbamylase deficiency (Grompe 1991, Wilnai 2018). This variant is reported in ClinVar (Variation ID: 97292), and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Grompe M et al. Improved molecular diagnostics for ornithine transcarbamylase deficiency. Am J Hum Genet. 1991 Feb;48(2):212-22. Wilnai Y et al. Prenatal treatment of ornithine transcarbamylase deficiency. Mol Genet Metab. 2018 Mar;123(3):297-300.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001802797	SCV002238574	pathogenic	Ornithine carbamoyltransferase deficiency	2022-08-03	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 97292). This premature translational stop signal has been observed in individual(s) with ornithine transcarbamylase deficiency (PMID: 1671317, 18604903). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg23*) in the OTC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTC are known to be pathogenic (PMID: 10946359, 16786505).
GeneDx	RCV000083537	SCV003852982	pathogenic	not provided	2023-03-31	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10946359, 24485820, 1671317, 18604903, 29396029, 9286441, 11793468, 11117428, 25433810, 19138872, 33489762, 33309754, 33272297, 32778825)
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001802797	SCV005417154	pathogenic	Ornithine carbamoyltransferase deficiency		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PS2_Moderate+PS4
GenMed Metabolism Lab	RCV000083537	SCV000115623	pathogenic	not provided		no assertion criteria provided	not provided	Converted during submission to Pathogenic.