Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003611136 | SCV004471539 | pathogenic | Pigmentary pallidal degeneration | 2022-12-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu563 amino acid residue in PANK2. Other variant(s) that disrupt this residue have been observed in individuals with PANK2-related conditions (PMID: 28881514, 33853092; Invitae), 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) performed at Invitae indicates that this missense variant is expected to disrupt PANK2 protein function. This missense change has been observed in individual(s) with PANK2-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 563 of the PANK2 protein (p.Leu563His). |