ClinVar Miner

Submissions for variant NM_152296.5(ATP1A3):c.2266C>T (p.Arg756Cys) (rs1064797245)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624914 SCV000741354 pathogenic Inborn genetic diseases 2016-02-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488196 SCV000575190 likely pathogenic not provided 2016-09-30 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000501825 SCV000593519 likely pathogenic Alternating hemiplegia of childhood 2 2016-06-15 criteria provided, single submitter clinical testing
Invitae RCV000692668 SCV000820504 pathogenic Dystonia 12 2018-04-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 756 of the ATP1A3 protein (p.Arg756Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in several individuals affected with rapid onset of ataxia, encephalopathy, dystonia, and weakness following a febrile illness (PMID: 27634470, 26400718, 27268479, 29066118). This variant has also been found to segregate with disease in 2 families (PMID: 29397530, 27726050). ClinVar contains an entry for this variant (Variation ID: 425189). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

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.