Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000522440 | SCV000617838 | uncertain significance | not provided | 2017-09-14 | criteria provided, single submitter | clinical testing | The R332Q variant was identified in two unrelated families with clinical and biochemical features suggestive of hereditary coproporphyria (HCP) (Gorman et al., 2008; Ma et al., 2011). In both families, the R332Q variant was identified in several individuals with acute episodes of porphyria symptoms, some of whom responded to treatment with heme arginate infusions, and was also detected in unaffected family members (Gorman et al., 2008; Ma et al., 2011; Rudd et al., 2013). The R332Q variant is not observed at significance frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). It is a semi-conservative amino acid substitution that occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant |
| Invitae | RCV000522440 | SCV000963765 | pathogenic | not provided | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 332 of the CPOX protein (p.Arg332Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with coproporphyria (PMID: 18557518, 23582006; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 449558). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CPOX protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |