ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.443T>C (p.Leu148Ser) (rs67016166)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001420869 SCV001623289 uncertain significance not specified 2021-05-17 criteria provided, single submitter clinical testing Variant summary: OTC c.443T>C (p.Leu148Ser) results in a non-conservative amino acid change located in the Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding domain (IPR006132) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 182681 control chromosomes (gnomAD). c.443T>C has been reported in the literature in individuals affected with Ornithine Transcarbamylase Deficiency including one de novo occurrence (Yamaguchi_2006, Azevedo_2006). These data indicate that the variant may be associated with disease. Additionally, two different amino acid substitutions at this position, p.Leu148Trp and p.Leu148Phe, have been found in OTCD patients and p.Leu148Phe results in reducing enzyme activity, supporting the clinical significance of this amino acid position. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
GenMed Metabolism Lab RCV000083439 SCV000115525 pathogenic not provided no assertion criteria provided not provided Converted during submission to Pathogenic.

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