Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001851533 | SCV002262684 | likely pathogenic | Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78 | 2023-03-14 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects ATP13A2 function (PMID: 22768177, 22847264, 23499937). 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. 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. ClinVar contains an entry for this variant (Variation ID: 1221). This missense change has been observed in individuals with clinical features of Kufor-Rakeb syndrome or hereditary spastic paraplegia (PMID: 17485642; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 504 of the ATP13A2 protein (p.Gly504Arg). |
| Mendelics | RCV000001280 | SCV002518548 | pathogenic | Kufor-Rakeb syndrome | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV002251851 | SCV002523272 | uncertain significance | See cases | 2019-10-04 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2, PP3 |
| OMIM | RCV000001280 | SCV000021430 | pathogenic | Kufor-Rakeb syndrome | 2007-05-08 | no assertion criteria provided | literature only |