ClinVar Miner

Submissions for variant NM_000375.3(UROS):c.217T>C (p.Cys73Arg) (rs121908012)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726590 SCV000345710 pathogenic not provided 2016-08-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000003948 SCV000361370 pathogenic Congenital erythropoietic porphyria 2017-04-27 criteria provided, single submitter clinical testing Across a selection of the available literature, the UROS c.217T>C (p.Cys73Arg) missense variant has been identified in 17 individuals with congenital erythropoietic porphyria, including in six in a homozygous state, in seven in a compound heterozygous state, and in four in a heterozygous state (Deybach et al. 1990; Boulechfar et al. 1992; Warner et al. 1992; Xu et al. 1995; Frank et al. 1998). The p.Cys73Arg variant was also found in a heterozygous state in ten unaffected family members (Deybach et al. 1990; Boulechfar et al. 1992; Warner et al. 1992; Xu et al. 1995; Frank et al. 1998). The variant was absent from the only two controls tested and is reported at a frequency of 0.00069 in the European American population of the Exome Sequencing Project. Expression of the p.Cys73Arg variant in E. coli showed less than 2% residual protein activity (Boulechfar et al. 1992; Warner et al. 1992). Fortian et al. (2011) demonstrated that the p.Cys73Arg variant leads to irreversible enzyme unfolding and aggregation while Bishop et al. (2011) showed that knock-in mice homozygous for the p.Cys73Arg variant had a severe phenotype. Based on the collective evidence, the p.Cys73Arg variant is classified as pathogenic for congenital erythropoietic porphyria. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000003948 SCV000024113 pathogenic Congenital erythropoietic porphyria 2011-04-15 no assertion criteria provided literature only
GeneReviews RCV000003948 SCV000086780 pathologic Congenital erythropoietic porphyria 2013-09-12 no assertion criteria provided curation Converted during submission to Pathogenic.

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