ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.482A>G (p.Asn161Ser) (rs72556271)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GenMed Metabolism Lab RCV000083455 SCV000115541 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.
GeneDx RCV000083455 SCV000517320 pathogenic not provided 2015-05-22 criteria provided, single submitter clinical testing The N161S missense variant in the OTC gene has been reported previously in associationwith OTC deficiency (Tuchman and Plante, 1995; Lipskind et al. 2011). Approximately20% of females who are heterozygous for variants in the OTC gene are clinicallysymptomatic with disease severity similar to males with partial deficiency (Yamaguchi etal., 2006; Tuchman et al., 2002). Therefore, we interpret the N161S variant as pathogenic.
Invitae RCV000793302 SCV000932650 pathogenic Ornithine carbamoyltransferase deficiency 2018-07-18 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 161 of the OTC protein (p.Asn161Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with ornithine transcarbamylase deficiency (PMID: 8786061, 12083811, 11388595, 21956151, 25994866). ClinVar contains an entry for this variant (Variation ID: 97216). Experimental studies have shown that this missense change has no residual enzyme activity in transfected COS-7 cells (PMID: 17041896). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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