Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000816933 | SCV000957462 | pathogenic | not provided | 2023-11-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 232 of the PPOX protein (p.Gly232Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with variegate porphyria (PMID: 8852667, 10486317, 12655566, 18570668). This variant is also known as c.971G>C. ClinVar contains an entry for this variant (Variation ID: 8693). 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 PPOX protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PPOX function (PMID: 11929051, 21048046). This variant disrupts the p.Gly232 amino acid residue in PPOX. Other variant(s) that disrupt this residue have been observed in individuals with PPOX-related conditions (PMID: 16433813), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000009230 | SCV000029448 | pathogenic | Variegate porphyria | 1996-03-01 | no assertion criteria provided | literature only |