ClinVar Miner

Submissions for variant NM_001395413.1(POR):c.1697G>A (p.Cys566Tyr)

gnomAD frequency: 0.00002  dbSNP: rs28931607
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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 RCV001553652 SCV001774589 likely pathogenic Congenital adrenal hyperplasia 2023-03-24 criteria provided, single submitter clinical testing Variant summary: POR c.1697G>A/p.Cys566Tyr (legacy name: c.1706G>A) results in a non-conservative amino acid change located in the Oxidoreductase FAD/NAD(P)-binding domain (IPR001433) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5e-06 in 201454 control chromosomes (gnomAD and publication data). c.1697G>A has been reported in the literature in one individual with amenorrhea and disordered steroidogenesis and two individuals affected with P450 Oxidoreductase Deficiency (Fluck_2004, Krine_2012, Reisch_2013). These data indicate that the variant may be associated with disease. Several functional studies report this variant disrupts NADPH binding and also has severe effects in many P450 based assays (Fluck_2004, Miller_2004, Huang_2005). 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 likely pathogenic.
OMIM RCV000018402 SCV000038684 pathogenic Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency 2004-06-26 no assertion criteria provided literature only

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