Submissions for variant NM_001958.5(EEF1A2):c.370G>A (p.Glu124Lys)

dbSNP: rs886042041

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000332862	SCV000330878	pathogenic	not provided	2018-06-04	criteria provided, single submitter	clinical testing	The E124K variant in the EEF1A2 gene has been reported previously as a de novo variant in an individual with epilepsy and developmental delay (Lam et al., 2016). The E124K variant is not observed in large population cohorts (Lek et al., 2016). The E124K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret E124K as a pathogenic variant.
CeGaT Center for Human Genetics Tuebingen	RCV000332862	SCV000780722	likely pathogenic	not provided	2018-02-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000703667	SCV000832577	pathogenic	Developmental and epileptic encephalopathy, 33	2024-03-02	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 124 of the EEF1A2 protein (p.Glu124Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of developmental and epileptic encephalopathy (PMID: 27441201, 33004838; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 280924). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on EEF1A2 protein function. For these reasons, this variant has been classified as Pathogenic.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000703667	SCV000965748	likely pathogenic	Developmental and epileptic encephalopathy, 33	2015-01-01	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Strasbourg University Hospital	RCV001260699	SCV001437791	likely pathogenic	Intellectual disability	2020-09-10	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002502091	SCV002811081	likely pathogenic	Intellectual disability, autosomal dominant 38; Developmental and epileptic encephalopathy, 33	2021-07-06	criteria provided, single submitter	clinical testing
Department of Genetics, Robert DEBRE University Hospital	RCV000332862	SCV004171544	pathogenic	not provided	2018-04-26	no assertion criteria provided	clinical testing