Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000434987 | SCV000524892 | uncertain significance | not provided | 2018-11-13 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ATP1A2 gene. The T620R variant has not beenpublished as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observedin approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome SequencingProject, indicating it is not a common benign variant in these populations. The T620R variant is a semi-conservativeamino acid substitution, which may impact secondary protein structure as these residues differ in some properties.This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant isprobably damaging to the protein structure/function. Based on the currently available information, it is unclearwhether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000470321 | SCV000544731 | uncertain significance | Familial hemiplegic migraine | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 620 of the ATP1A2 protein (p.Thr620Arg). This variant is not present in population databases (gnomAD no frequency). 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: 384176). 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 with a positive predictive value of 80%. 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. |
| Fulgent Genetics, |
RCV002488923 | SCV002791129 | uncertain significance | Alternating hemiplegia of childhood 1; Migraine, familial hemiplegic, 2; Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies; Developmental and epileptic encephalopathy 98 | 2022-04-01 | criteria provided, single submitter | clinical testing |