ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.712C>T (p.Arg238Cys)

dbSNP: rs1558004341
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002316178 SCV000847816 uncertain significance Inborn genetic diseases 2016-09-10 criteria provided, single submitter clinical testing The p.R238C variant (also known as c.712C>T), located in coding exon 7 of the ATP1A2 gene, results from a C to T substitution at nucleotide position 712. The arginine at codon 238 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. 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.
Invitae RCV000716971 SCV001407758 uncertain significance Familial hemiplegic migraine 2022-12-02 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 238 of the ATP1A2 protein (p.Arg238Cys). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 588262). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. 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. 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 ATP1A2 protein function.
GeneDx RCV003128658 SCV003805019 uncertain significance not provided 2022-08-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Preventiongenetics, part of Exact Sciences RCV003411654 SCV004106811 uncertain significance ATP1A2-related condition 2023-09-03 criteria provided, single submitter clinical testing The ATP1A2 c.712C>T variant is predicted to result in the amino acid substitution p.Arg238Cys. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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