Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003502043 | SCV004298016 | pathogenic | Pigmentary pallidal degeneration | 2022-11-11 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs768230831, gnomAD 0.002%). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 322 of the PANK2 protein (p.Glu322Gly). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Glu322 amino acid residue in PANK2. Other variant(s) that disrupt this residue have been observed in individuals with PANK2-related conditions (PMID: 16437574), which suggests that this may be a clinically significant amino acid residue. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PANK2 protein function. This variant is also known as 635A>G E212G. This missense change has been observed in individual(s) with neurodegeneration with brain iron accumulation (PMID: 12510040, 15911822, 16437574, 22221393). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. |
| Fulgent Genetics, |
RCV003502043 | SCV005656905 | likely pathogenic | Pigmentary pallidal degeneration | 2024-01-04 | criteria provided, single submitter | clinical testing |