Submissions for variant NM_000531.6(OTC):c.533C>T (p.Thr178Met)

dbSNP: rs72556284

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000083477	SCV000490676	pathogenic	not provided	2020-12-07	criteria provided, single submitter	clinical testing	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: 25958381, 23430554, 16786505, 9452049, 29524203, 11117428, 25994866, 7860066, 25433810, 10946359, 24007980, 18662894, 23829977, 15159648, 17334707, 17565723, 12083811, 23231960, 28324312, 31426867)
Institute of Human Genetics, University of Leipzig Medical Center	RCV001262181	SCV001439962	pathogenic	Ornithine carbamoyltransferase deficiency	2019-01-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001262181	SCV002033221	pathogenic	Ornithine carbamoyltransferase deficiency	2021-11-07	criteria provided, single submitter	clinical testing
Invitae	RCV001262181	SCV002185534	pathogenic	Ornithine carbamoyltransferase deficiency	2022-06-13	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 178 of the OTC protein (p.Thr178Met). 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: 97237). This missense change has been observed in individual(s) with ornithine transcarbamylase deficiency (PMID: 7860066). This variant is not present in population databases (gnomAD no frequency).
Athena Diagnostics Inc	RCV000083477	SCV002817188	pathogenic	not provided	2021-10-04	criteria provided, single submitter	clinical testing	This variant appeared to occur de novo in an individual tested at Athena Diagnostics with clinical features associated with this gene. This variant has been identified in multiple unrelated individuals with clinical features associated with this gene (PMID: 7860066, 23829977, 25994866, 12083811, 31426867, 17334707, 34014569, 17565723, 29524203, 10946359, 9452049, 11117428, 23430554). This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Computational tools yielded predictions that this amino acid change may be damaging to the protein.This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study.
Revvity Omics, Revvity	RCV001262181	SCV004237391	pathogenic	Ornithine carbamoyltransferase deficiency	2023-08-13	criteria provided, single submitter	clinical testing
GenMed Metabolism Lab	RCV000083477	SCV000115563	pathogenic	not provided		no assertion criteria provided	not provided	Converted during submission to Pathogenic.