Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000686300 | SCV000813812 | uncertain significance | Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78 | 2022-05-12 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 754 of the ATP13A2 protein (p.Leu754Val). This variant is present in population databases (rs139909551, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ATP13A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 566479). 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 not expected to disrupt ATP13A2 protein function. 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 | RCV002442419 | SCV002737844 | uncertain significance | Inborn genetic diseases | 2019-04-05 | criteria provided, single submitter | clinical testing | The p.L754V variant (also known as c.2260C>G), located in coding exon 21 of the ATP13A2 gene, results from a C to G substitution at nucleotide position 2260. The leucine at codon 754 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |