ClinVar Miner

Submissions for variant NM_000375.3(UROS):c.244G>T (p.Val82Phe) (rs121908016)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000003956 SCV000361369 uncertain significance Congenital erythropoietic porphyria 2017-04-28 criteria provided, single submitter clinical testing The UROS c.244G>T (p.Val82Phe) missense variant has been reported in two studies in which it was found in two individuals with congenital erythropoietic porphyria including in one patient in a compound heterozygous state and in a second patient in a heterozygous state in whom a second variant was not found (Xu et al. 1995; Katugampola et al. 2012). Control data are not available for this variant which is reported at a frequency of 0.00003 in the European (non-Finnish) population of the Exome Aggregation Consortium. This frequency is based on two alleles only in a region of good sequence coverage so the variant is presumed rare. In a functional study by Xu et al. (1995) the p.Val82Phe variant enzyme was expressed in E. coli and demonstrated to have 35.8% residual activity and less thermostability compared to wild type. However, in a similar study by Fortian et al. (2009), the variant was shown to have 93.8% of the specific activity of wild type with no decrease in stability. RNA analysis showed that the p.Val82Phe variant produced two RNA species, one of normal size and one shorter product which was the result of a deletion of exon four. The shorter product accounted for 53.8% of the total RNA produced (Xu et al. 1995). The Val82 residue is not conserved between human and mouse (Xu et al. 1996). Based on the evidence, the p.Val82Phe variant is considered to be a variant of unknown significance, but suspicious for pathogenicity for congenital erythropoietic porphyria. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000003956 SCV000024121 pathogenic Congenital erythropoietic porphyria 1995-02-01 no assertion criteria provided literature only
GeneReviews RCV000003956 SCV000086781 pathologic Congenital erythropoietic porphyria 2013-09-12 no assertion criteria provided curation Converted during submission to Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.