ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.1282C>T (p.Arg428Cys)

gnomAD frequency: 0.00001  dbSNP: rs779985796
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000445337 SCV000529335 uncertain significance not provided 2016-06-27 criteria provided, single submitter clinical testing The R428C variant in the ATP1A2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. It was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.The R428C variant is a non-conservative amino acid substitution that occurs at a conserved position in the cytoplasmic domain. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R428C as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV000763747 SCV000894633 uncertain significance Alternating hemiplegia of childhood 1; Migraine, familial hemiplegic, 2 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV003362785 SCV004084805 uncertain significance Inborn genetic diseases 2023-07-25 criteria provided, single submitter clinical testing The c.1282C>T (p.R428C) alteration is located in exon 10 (coding exon 10) of the ATP1A2 gene. This alteration results from a C to T substitution at nucleotide position 1282, causing the arginine (R) at amino acid position 428 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003584601 SCV004317961 uncertain significance Familial hemiplegic migraine 2023-04-29 criteria provided, single submitter clinical testing 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. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 428 of the ATP1A2 protein (p.Arg428Cys). This variant is present in population databases (rs779985796, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 387342). 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 expected to disrupt ATP1A2 protein function.

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