Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001779503 | SCV002015030 | uncertain significance | not specified | 2021-10-22 | criteria provided, single submitter | clinical testing | Variant summary: PANK2 c.1607A>G (p.Tyr536Cys) results in a non-conservative amino acid change located in the catalytic core (211-570 aa, Pan_2013) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 252688 control chromosomes (gnomAD and publication data). c.1607A>G has been reported in the literature in individuals affected with Pantothenate Kinase-Associated Neurodegeneration (Lim_2011, Pan_2013). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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 VUS-possibly pathogenic. |
| Invitae | RCV003502606 | SCV004298029 | pathogenic | Pigmentary pallidal degeneration | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 536 of the PANK2 protein (p.Tyr536Cys). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with PANK2-related conditions (PMID: 22103354, 35246191). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1321409). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |