ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.505C>G (p.Pro169Ala) (rs72556277)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000813314 SCV000953672 likely pathogenic Ornithine carbamoyltransferase deficiency 2018-11-06 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 169 of the OTC protein (p.Pro169Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with clinical features of ornithine transcarbamylase deficiency (PMID: 11793468). ClinVar contains an entry for this variant (Variation ID: 97227). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Pro169 amino acid residue in OTC. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 11117428, 26059767), which suggests that this may be a clinically significant amino acid residue. 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.
GenMed Metabolism Lab RCV000083467 SCV000115553 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.

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