Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000397500 | SCV000350109 | uncertain significance | Variegate porphyria | 2017-04-28 | criteria provided, single submitter | clinical testing | The PPOX c.1303C>T (p.Gln435Ter) variant is a stop-gained variant that is predicted to result in premature termination of the protein. The p.Gln435Ter variant has been reported in two studies, both with limited information. Whatley et al. (1999) detected the p.Gln435Ter variant in five families, but no details were provided regarding the number of affected individuals or zygosity of the variant. In a second study, Frank et al. (2001) reported the presence of p.Gln435Ter variant in one affected individual and their two sons of unknown affected status, with no details of zygosity given. The p.Gln435Ter variant was absent from 200 control chromosomes (Frank et al. 2001), and is reported at a frequency of 0.00002 in the European (non-Finnish) population of the Exome Aggregation Consortium, but this is based on only one allele so the variant is presumed to be rare. Based on the limited evidence and the potential impact of stop-gained variants, the p.Gln435Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for variegate porphyria. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Labcorp Genetics |
RCV001063622 | SCV001228479 | pathogenic | not provided | 2023-01-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 293260). This premature translational stop signal has been observed in individuals with variegate porphyria (PMID: 10486317, 11348478). This variant is present in population databases (rs754313121, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Gln435*) in the PPOX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 43 amino acid(s) of the PPOX protein. |
Mayo Clinic Laboratories, |
RCV001063622 | SCV004226537 | likely pathogenic | not provided | 2023-02-15 | criteria provided, single submitter | clinical testing | PP4, PM2, PVS1_strong |