Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000003956 | SCV000361369 | uncertain significance | Cutaneous 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. |
| Mayo Clinic Laboratories, |
RCV003480019 | SCV004225341 | uncertain significance | not provided | 2022-06-22 | criteria provided, single submitter | clinical testing | PP3, PM2, PM3_supporting, PS3_supporting |
| OMIM | RCV000003956 | SCV000024121 | pathogenic | Cutaneous porphyria | 1995-02-01 | no assertion criteria provided | literature only | |
| Gene |
RCV000003956 | SCV000086781 | not provided | Cutaneous porphyria | no assertion provided | literature only |