Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001924514 | SCV002148577 | uncertain significance | Pigmentary pallidal degeneration | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 430 of the PANK2 protein (p.Thr430Ala). This variant is not present in population databases (gnomAD no frequency). 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: 1383145). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002552857 | SCV003590445 | uncertain significance | Inborn genetic diseases | 2024-03-01 | criteria provided, single submitter | clinical testing | The c.1288A>G (p.T430A) alteration is located in exon 4 (coding exon 4) of the PANK2 gene. This alteration results from a A to G substitution at nucleotide position 1288, causing the threonine (T) at amino acid position 430 to be replaced by an alanine (A). Based on data from gnomAD, the G allele has an overall frequency of <0.001% (1/251464) total alleles studied. The highest observed frequency was 0.006% (1/16256) of African alleles. This amino acid position is well conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |