Submissions for variant NM_152296.5(ATP1A3):c.1838C>T (p.Thr613Met)

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726724	SCV000702441	pathogenic	not provided	2016-11-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000013772	SCV000827091	pathogenic	Dystonia 12	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 613 of the ATP1A3 protein (p.Thr613Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with rapid onset dystonia parkinsonism (RDP) (PMID: 15260953, 17282997, 17516473, 22534615, 24523486). 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. ClinVar contains an entry for this variant (Variation ID: 12909). 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 ATP1A3 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ATP1A3 function (PMID: 15260953). For these reasons, this variant has been classified as Pathogenic.
Mendelics	RCV000013772	SCV001141094	pathogenic	Dystonia 12	2019-05-28	criteria provided, single submitter	clinical testing
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV001004717	SCV001164184	pathogenic	Alternating hemiplegia of childhood 2	2017-08-10	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000013772	SCV001428887	pathogenic	Dystonia 12	2018-04-27	criteria provided, single submitter	clinical testing
Centogene AG - the Rare Disease Company	RCV000013772	SCV002059395	pathogenic	Dystonia 12	2020-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000726724	SCV002520184	pathogenic	not provided	2022-05-15	criteria provided, single submitter	clinical testing	Functional studies indicate that T613M interferes with hydrogen bonding near the catalytic site (Rodacker et al., 2006, de Carvalho Aguiar et al., 2004).; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11061257, 17595045, 22850527, 24842602, 15390049, 15260953, 12112218, 29801903, 24523486, 17516473, 30097153, 31061839, 31361359, 33326973, 32653672, Post2009[Article], 17282997, 22534615, 16632466)
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000013772	SCV002764804	pathogenic	Dystonia 12	2021-02-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University Hospital of Duesseldorf	RCV000013772	SCV004171126	pathogenic	Dystonia 12		criteria provided, single submitter	not provided
OMIM	RCV000013772	SCV000034019	pathogenic	Dystonia 12	2007-03-01	no assertion criteria provided	literature only
GeneReviews	RCV000013772	SCV000041595	not provided	Dystonia 12		no assertion provided	literature only