ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.1499-1G>C

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Total submissions: 1
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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 RCV001192546 SCV001360760 pathogenic Propionic acidemia 2021-05-09 criteria provided, single submitter clinical testing Variant summary: PCCB c.1499-1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 3' splice acceptor site (ACMG PVS1 and PP3). However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251110 control chromosomes (ACMG PM2). c.1499-1G>C has been reported in the literature in at-least one individual affected with early onset Propionic Acidemia type B (PCCB) who was reportedly compound heterozygous for c.562G>A, p.G188R in the PCCB gene (ACMG PM3) (example, Perez_2003). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No other 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 pathogenic.

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