ClinVar Miner

Submissions for variant NM_001958.5(EEF1A2):c.364G>A (p.Glu122Lys)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000193799 SCV000247256 likely pathogenic Developmental and epileptic encephalopathy, 33 2015-02-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV000622866 SCV000742156 pathogenic Inborn genetic diseases 2017-02-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000193799 SCV000774988 pathogenic Developmental and epileptic encephalopathy, 33 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 122 of the EEF1A2 protein (p.Glu122Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurological disease, including epilepsy and intellectual disability (PMID: 24697219, 26682508, 27441201). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 192252). 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 EEF1A2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects EEF1A2 function (PMID: 3066688). For these reasons, this variant has been classified as Pathogenic.
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV000193799 SCV001164200 pathogenic Developmental and epileptic encephalopathy, 33 2018-10-25 criteria provided, single submitter clinical testing
Epilepsy Neurogenetics Initiative, Children's Hospital of Philadelphia RCV001030064 SCV001192844 pathogenic EEF1A2-related developmental and degenerative epileptic-dyskinetic encephalopathy 2020-02-13 criteria provided, single submitter research The EEF1A2 c.364G>A; p.Glu122Lys variant has been identified in three individuals with a developmental and epileptic encephalopathy characterized by global developmental delays, moderate to severe intellectual disability, and intractable infantile or early childhood onset epilepsy. One individual had a hyperkinetic movement disorder characterized by choreoathetosis. The variant is confirmed de novo in two individuals; testing of both parents was not performed in the third individual. The variant is absent from population databases (ExAC, gnomAD) and is predicted to have a damaging effect on the protein by in silico models. Therefore, this variant has been classified as pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001267946 SCV001446465 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Laboratoire de Génétique Moléculaire, CHU Bordeaux RCV001267946 SCV001468930 pathogenic not provided criteria provided, single submitter clinical testing
Baylor Genetics RCV000172840 SCV001529140 pathogenic Intellectual disability, autosomal dominant 38 2018-10-04 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease causing [PMID 24697219, 26682508, 27441201]
CeGaT Center for Human Genetics Tuebingen RCV001267946 SCV001746716 pathogenic not provided 2021-05-01 criteria provided, single submitter clinical testing
GeneDx RCV001267946 SCV001815518 pathogenic not provided 2020-10-13 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32196822, 31477274, 27441201, 23033978, 23647072, 26740508, 19636410, 28911200, 28378778, 24697219, 3066688, 26682508)
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000193799 SCV004045930 pathogenic Developmental and epileptic encephalopathy, 33 2023-03-08 criteria provided, single submitter clinical testing
OMIM RCV000172840 SCV000223806 pathogenic Intellectual disability, autosomal dominant 38 2015-04-01 no assertion criteria provided literature only
Department of Genetics, Robert DEBRE University Hospital RCV001267946 SCV004171547 pathogenic not provided 2018-04-26 no assertion criteria provided clinical testing

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