Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000423915 | SCV000530123 | uncertain significance | not provided | 2016-08-01 | criteria provided, single submitter | clinical testing | The V1093L variant in the ATP13A2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V1093L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V1093L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V1093L as a variant of uncertain significance. |
Invitae | RCV000794087 | SCV000933473 | uncertain significance | Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78 | 2018-08-21 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with leucine at codon 1093 of the ATP13A2 protein (p.Val1093Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ATP13A2-related disease. ClinVar contains an entry for this variant (Variation ID: 387937). This variant is not present in population databases (ExAC no frequency). |