Description
This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 234 of the PANK2 protein (p.Thr234Ala). This variant is present in population databases (rs137852965, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of pantothenate kinase-associated neurodegeneration (PMID: 11479594, 16023068, 26547561). This variant is also known as c.400A>G (p.T124A) or c.370A>G. ClinVar contains an entry for this variant (Variation ID: 4554). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PANK2 protein function. Experimental studies have shown that this missense change does not substantially affect PANK2 function (PMID: 15659606). This variant disrupts the p.Thr234 amino acid residue in PANK2. Other variant(s) that disrupt this residue have been observed in individuals with PANK2-related conditions (PMID: 23166001), which suggests that this may be a clinically significant amino acid residue. 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.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
