Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000355680 | SCV000433816 | uncertain significance | Pigmentary pallidal degeneration | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV000355680 | SCV001373361 | likely pathogenic | Pigmentary pallidal degeneration | 2023-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 440 of the PANK2 protein (p.Arg440Cys). This variant is present in population databases (rs201329683, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PANK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 338363). 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%. This variant disrupts the p.Arg440 amino acid residue in PANK2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27303611, 33043782). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV002523160 | SCV003738480 | uncertain significance | Inborn genetic diseases | 2022-05-26 | criteria provided, single submitter | clinical testing | The c.1318C>T (p.R440C) alteration is located in exon 4 (coding exon 4) of the PANK2 gene. This alteration results from a C to T substitution at nucleotide position 1318, causing the arginine (R) at amino acid position 440 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |