ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.118C>T (p.Arg40Cys) (rs72554307)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000011760 SCV000893833 likely pathogenic Ornithine carbamoyltransferase deficiency 2018-10-31 criteria provided, single submitter clinical testing
GenMed Metabolism Lab RCV000083332 SCV000115418 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.
Invitae RCV000011760 SCV000756189 likely pathogenic Ornithine carbamoyltransferase deficiency 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 40 of the OTC protein (p.Arg40Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with ornithine transcarbamylase deficiency and hyperammonemia (PMID: 23209112, 7860066, Invitae). ClinVar contains an entry for this variant (Variation ID: 11013). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Arg40His) has been determined to be pathogenic (PMID: 7860066, 8863155, 11793468, 21070677, 23209112). This suggests that the arginine residue is critical for OTC protein function and that other missense substitutions at this position may also be pathogenic. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000011760 SCV000031992 pathogenic Ornithine carbamoyltransferase deficiency 2001-02-01 no assertion criteria provided literature only

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