Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003236339 | SCV003934221 | pathogenic | Pigmentary pallidal degeneration | 2023-05-12 | criteria provided, single submitter | clinical testing | Variant summary: PANK2 c.1502T>A (p.Ile501Asn) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251468 control chromosomes (gnomAD). c.1502T>A has been reported in the literature in multiple compound heterozygous individuals as well as at least one homozygous individual affected with Pantothenate Kinase-Associated Neurodegeneration (e.g., Zhang_2005, Lim_2012, Chang_2020). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 32310012, 22103354, 15747360). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV003236339 | SCV004298025 | pathogenic | Pigmentary pallidal degeneration | 2023-02-25 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 501 of the PANK2 protein (p.Ile501Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pantothenate kinase-associated neurodegeneration (PMID: 22103354, 32310012). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as p.Ile391Asn. 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. For these reasons, this variant has been classified as Pathogenic. |