Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000801260 | SCV000941031 | likely benign | Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78 | 2023-08-30 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001097440 | SCV001253722 | uncertain significance | Kufor-Rakeb syndrome | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Ambry Genetics | RCV002458463 | SCV002615369 | uncertain significance | Inborn genetic diseases | 2018-07-16 | criteria provided, single submitter | clinical testing | The p.T12M variant (also known as c.35C>T), located in coding exon 2 of the ATP13A2 gene, results from a C to T substitution at nucleotide position 35. The threonine at codon 12 is replaced by methionine, an amino acid with similar properties. This variant has been reported in multiple individuals with Parkinson disease (Di Fonzo A et al. Neurology, 2007 May;68:1557-62; Li G et al. Med. Sci. Monit., 2014 Nov;20:2177-82; Petersen MS et al. Parkinsonism Relat. Disord., 2015 Jan;21:75-8). Functional studies of this variant demonstrated that the T12M mutant protein does not have significant effect on protein stability or subcellular localization, but reduces the ATPase activity of microsomal ATP13A2 (Podhajska A et al. PLoS ONE, 2012 Jun;7:e39942; Matsui H et al. FEBS Lett., 2013 May;587:1316-25). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |