Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000796885 | SCV000936418 | uncertain significance | Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78 | 2022-07-23 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 999 of the ATP13A2 protein (p.Val999Met). This variant is present in population databases (rs764162255, gnomAD 0.06%). 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: 643225). 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 | RCV002440645 | SCV002747002 | uncertain significance | Inborn genetic diseases | 2018-06-13 | criteria provided, single submitter | clinical testing | The p.V999M variant (also known as c.2995G>A), located in coding exon 26 of the ATP13A2 gene, results from a G to A substitution at nucleotide position 2995. The valine at codon 999 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and methionine is the reference amino acid in other 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. |