ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.422G>A (p.Arg141Gln)

dbSNP: rs68026851
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000083434 SCV000230943 pathogenic not provided 2015-05-19 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000011734 SCV000894489 pathogenic Ornithine carbamoyltransferase deficiency 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000011734 SCV001212429 pathogenic Ornithine carbamoyltransferase deficiency 2022-10-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt OTC protein function. ClinVar contains an entry for this variant (Variation ID: 10987). This variant is also known as Arg109Gln. This missense change has been observed in individuals with ornithine transcarbamylase deficiency (PMID: 3170748, 8830175, 8985493, 30175132). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 141 of the OTC protein (p.Arg141Gln).
GeneDx RCV000083434 SCV001802043 pathogenic not provided 2020-12-09 criteria provided, single submitter clinical testing Published functional studies that R141Q is associated with significantly reduced OTC activity compared to wild-type (Lee et al., 1989; Augustin et al., 2000).; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33272297, 31589614, 28324312, 8985493, 8830175, 17044854, 1757964, 3170748, 1627356, 2556444, 11102556, 30175132)
Genome-Nilou Lab RCV000011734 SCV002033219 pathogenic Ornithine carbamoyltransferase deficiency 2021-11-07 criteria provided, single submitter clinical testing
OMIM RCV000011734 SCV000031966 pathogenic Ornithine carbamoyltransferase deficiency 1992-06-01 no assertion criteria provided literature only
GenMed Metabolism Lab RCV000083434 SCV000115520 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.