Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000004810 | SCV002305227 | pathogenic | Pigmentary pallidal degeneration | 2023-09-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 264 of the PANK2 protein (p.Arg264Trp). This variant is present in population databases (rs137852961, gnomAD 0.01%). This missense change has been observed in individuals with pantothenate kinase-associated neurodegeneration (PMID: 11479594, 16437574, 22221393). This variant is also known as p.R154W . ClinVar contains an entry for this variant (Variation ID: 4550). 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 variant disrupts the p.Arg264 amino acid residue in PANK2. Other variant(s) that disrupt this residue have been observed in individuals with PANK2-related conditions (PMID: 16437574, 33098801), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV002460885 | SCV002757691 | likely pathogenic | not provided | 2022-05-27 | criteria provided, single submitter | clinical testing | Observed multiple times with a second PANK2 variant in unrelated patients with PANK2-related neurodegeneration in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes in all cases (Darling et al., 2017; Hartig et al., 2006; Zhou et al., 2001); Published functional studies demonstrate that the variant results in a significant decrease in PANK2 protein activity (Hong et al., 2007; Zhang et al., 2006); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31540697, 27544236, 32928263, 28456385, 22221393, 11479594, 32456086, 16272150, 16437574, 28845923, 17631502) |
OMIM | RCV000004810 | SCV000024986 | pathogenic | Pigmentary pallidal degeneration | 2001-08-01 | no assertion criteria provided | literature only |