ClinVar Miner

Submissions for variant NM_022089.4(ATP13A2):c.373G>C (p.Ala125Pro)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002349234 SCV002621225 uncertain significance Inborn genetic diseases 2019-01-31 criteria provided, single submitter clinical testing The p.A125P variant (also known as c.373G>C), located in coding exon 5 of the ATP13A2 gene, results from a G to C substitution at nucleotide position 373. The alanine at codon 125 is replaced by proline, an amino acid with highly similar properties. This amino acid position is poorly conserved in available 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003094339 SCV003277825 uncertain significance Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78 2024-10-16 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 125 of the ATP13A2 protein (p.Ala125Pro). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 1734468). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ATP13A2 protein function with a negative predictive value of 95%. 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.

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