ClinVar Miner

Submissions for variant NM_012203.2(GRHPR):c.905G>C (p.Arg302Pro)

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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 RCV003317900 SCV004021089 uncertain significance not specified 2023-06-30 criteria provided, single submitter clinical testing Variant summary: GRHPR c.905G>C (p.Arg302Pro) results in a non-conservative amino acid change located in the catalytic domain (IPR006139) 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 251472 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.905G>C has been reported in the literature in at least one compound heterozygous individual affected with Primary Hyperoxaluria (e.g., Hopp_2015). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 25644115). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Additionally, other missense variants affecting this codon, namely c.904C>T (p.R302C) and c.905G>A (p.R302H), have been reported in the literature in patients with primary hyperoxaluria (PMIDs: 14635115, 35314707, 31685312); R302C has also been reported as pathogenic in ClinVar and functional studies found this variant resulted in severely reduced glyoxylate reductase activity (PMID: 14635115). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Rare Kidney Stone Consortium and the Mayo Clinic Hyperoxaluria Center, Mayo Clinic RCV003445232 SCV004171757 likely pathogenic Primary hyperoxaluria, type II 2023-10-27 criteria provided, single submitter clinical testing ACMG:PM1 PM2 PM3 PM5 PP3

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