ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.192G>T (p.Gln64His)

gnomAD frequency: 0.00001  dbSNP: rs796052282
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186812 SCV000240382 uncertain significance not provided 2022-03-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV000764992 SCV000896171 uncertain significance Alternating hemiplegia of childhood 1; Migraine, familial hemiplegic, 2 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000815024 SCV000955464 uncertain significance Familial hemiplegic migraine 2024-02-23 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 64 of the ATP1A2 protein (p.Gln64His). 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: 204910). 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 with a negative 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.
Ambry Genetics RCV002513979 SCV003666081 uncertain significance Inborn genetic diseases 2022-12-02 criteria provided, single submitter clinical testing The c.192G>T (p.Q64H) alteration is located in exon 4 (coding exon 4) of the ATP1A2 gene. This alteration results from a G to T substitution at nucleotide position 192, causing the glutamine (Q) at amino acid position 64 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004739572 SCV005367469 uncertain significance ATP1A2-related disorder 2024-08-06 no assertion criteria provided clinical testing The ATP1A2 c.192G>T variant is predicted to result in the amino acid substitution p.Gln64His. To our knowledge, this variant has not been reported in the literature or in a large population database, 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.