Submissions for variant NM_000531.6(OTC):c.621C>A (p.Ser207Arg)

dbSNP: rs72558415

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000083516	SCV002756892	likely pathogenic	not provided	2022-05-25	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); 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: 9452024, 28324312)
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV003225028	SCV003921989	likely pathogenic	Ornithine carbamoyltransferase deficiency	2021-05-07	criteria provided, single submitter	clinical testing	0102 - Loss of function is a known mechanism of disease in this gene and is associated with ornithine transcarbamylase deficiency. (I) 0109 - This gene is associated with X-linked recessive disease, however carrier females can be affected (PMID:26059767). (I) 0200 - Variant is predicted to result in a missense amino acid change from serine to arginine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated aspartate/ornithine carbamoyl transferase domain (Pfam). (I) 0703 - Other missense variants comparable to the one identified in this case have moderate previous evidence for pathogenicity. The variant p.(Ser207Asn) has been reported in multiple individuals with ornithine transcarbamylase deficiency (PMID: 17565723, 23278509, 16786505, ClinVar). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. Two individuals with ornithine transcarbamylase deficiency have been reported with this variant (PMID:9452024, ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
GenMed Metabolism Lab	RCV000083516	SCV000115602	pathogenic	not provided		no assertion criteria provided	not provided	Converted during submission to Pathogenic.