Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001943679 | SCV002188607 | uncertain significance | Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78 | 2021-10-11 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces arginine with glutamine at codon 1073 of the ATP13A2 protein (p.Arg1073Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs747907490, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with ATP13A2-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. |
| Ambry Genetics | RCV002557872 | SCV003584553 | uncertain significance | Inborn genetic diseases | 2021-09-27 | criteria provided, single submitter | clinical testing | The c.3218G>A (p.R1073Q) alteration is located in exon 27 (coding exon 27) of the ATP13A2 gene. This alteration results from a G to A substitution at nucleotide position 3218, causing the arginine (R) at amino acid position 1073 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |