Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000186810 | SCV000240380 | uncertain significance | not provided | 2014-09-09 | criteria provided, single submitter | clinical testing | p.Arg564Trp (CGG>TGG): c.1690 C>T in exon 13 of the ATP1A2 gene (NM_000702.3). The R564W variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 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 R564W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved across all species in evolution. Additionally, missense mutations in nearby residues have not been reported. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
| Fulgent Genetics, |
RCV000763748 | SCV000894634 | uncertain significance | Alternating hemiplegia of childhood 1; Migraine, familial hemiplegic, 2 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003165420 | SCV003897285 | uncertain significance | Inborn genetic diseases | 2023-02-15 | criteria provided, single submitter | clinical testing | The c.1690C>T (p.R564W) alteration is located in exon 13 (coding exon 13) of the ATP1A2 gene. This alteration results from a C to T substitution at nucleotide position 1690, causing the arginine (R) at amino acid position 564 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003746501 | SCV004519447 | uncertain significance | Familial hemiplegic migraine | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 564 of the ATP1A2 protein (p.Arg564Trp). This variant is present in population databases (rs762330744, gnomAD 0.01%). 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: 204908). 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. |
| Mayo Clinic Laboratories, |
RCV000186810 | SCV005408336 | uncertain significance | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | PP2 |