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

dbSNP: rs1064797245

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics 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
Ambry Genetics	RCV000624914	SCV000741354	pathogenic	Inborn genetic diseases	2016-02-16	criteria provided, single submitter	clinical testing
Invitae	RCV000692668	SCV000820504	pathogenic	Dystonia 12	2023-09-24	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 425189). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 756 of the ATP1A3 protein (p.Arg756Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with rapid onset of ataxia, encephalopathy, dystonia, and weakness following a febrile illness (PMID: 26400718, 27268479, 27634470, 27726050, 29066118, 29397530). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000850500	SCV000992700	likely pathogenic	Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome; Dystonia 12; Alternating hemiplegia of childhood 2	2018-10-12	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000488196	SCV001446978	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
GeneDx	RCV000488196	SCV001793155	pathogenic	not provided	2023-05-25	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29396171, 8496742, 27726050, 22842232, 34765691, 34761051, 34975730, 26400718, 24436111, 19652145, 24123283, 23483595, 27091223, 26297560, 25895915, 26410222, 28293679, 16632466, 22534615, 24739246, 24468074, 29184165, 25656163, 15260953, 24996492, 25359261, 22850527, 29397530, 28647130, 27634470, 27268479, 29346770, 29066118, 30862413, 31269555, 31737037, 32637629, 31216405, 31175295)
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV000501825	SCV002512690	pathogenic	Alternating hemiplegia of childhood 2	2021-07-15	criteria provided, single submitter	clinical testing	ACMG classification criteria: PS4 moderate, PM2 moderate, PM5, PM6 strong, PP1 moderate, PP3 supporting
Revvity Omics, Revvity	RCV000488196	SCV003811134	pathogenic	not provided	2022-03-29	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000692668	SCV003836469	pathogenic	Dystonia 12	2022-03-25	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University Hospital of Duesseldorf	RCV003335375	SCV004046815	pathogenic	Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000488196	SCV001739883	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000488196	SCV001952062	pathogenic	not provided		no assertion criteria provided	clinical testing
GeneReviews	RCV000692668	SCV002559236	not provided	Dystonia 12		no assertion provided	literature only