ClinVar Miner

Submissions for variant NM_022089.4(ATP13A2):c.595C>T (p.Arg199Cys)

gnomAD frequency: 0.00002  dbSNP: rs754074592
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001049143 SCV001213177 uncertain significance Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 199 of the ATP13A2 protein (p.Arg199Cys). This variant is present in population databases (rs754074592, gnomAD 0.01%). 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: 845963). 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. 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.
Ambry Genetics RCV002355031 SCV002656481 uncertain significance Inborn genetic diseases 2017-10-06 criteria provided, single submitter clinical testing The p.R199C variant (also known as c.595C>T), located in coding exon 7 of the ATP13A2 gene, results from a C to T substitution at nucleotide position 595. The arginine at codon 199 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and cysteine is the reference amino acid in other 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.

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