ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.586C>T (p.Arg196Cys)

gnomAD frequency: 0.00001  dbSNP: rs753517155
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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 RCV000820384 SCV000961093 uncertain significance Familial hemiplegic migraine 2024-04-05 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 196 of the ATP1A2 protein (p.Arg196Cys). This variant is present in population databases (rs753517155, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of ATP1A2-related conditions (PMID: 29062094; Invitae). ClinVar contains an entry for this variant (Variation ID: 662679). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ATP1A2 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 RCV002352452 SCV002654284 uncertain significance Inborn genetic diseases 2017-11-13 criteria provided, single submitter clinical testing The p.R196C variant (also known as c.586C>T), located in coding exon 6 of the ATP1A2 gene, results from a C to T substitution at nucleotide position 586. The arginine at codon 196 is replaced by cysteine, an amino acid with highly dissimilar properties. In one study, this alteration was detected in an individual with clinically-diagnosed episodic ataxia (Choi KD et al. Sci Rep, 2017 Oct;7:13855). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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