ClinVar Miner

Submissions for variant NM_001958.3(EEF1A2):c.1267C>T (p.Arg423Cys) (rs886039346)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000623478 SCV000742919 uncertain significance Inborn genetic diseases 2017-09-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
GeneDx RCV000255580 SCV000321583 pathogenic not provided 2016-08-09 criteria provided, single submitter clinical testing The R423C variant in the EEF1A2 gene has been reported previously as a de novo change in multiple individuals with epileptic encephalopathy (Helbig et al., 2015; Lam et al., 2016; Retterer et al., 2016). R423C 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.
Invitae RCV000688443 SCV000816053 likely pathogenic Epileptic encephalopathy, early infantile, 33 2018-01-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 423 of the EEF1A2 protein (p.Arg423Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported to be de novo in an individual affected with early infantile epileptic encephalopathy (PMID: 27441201). ClinVar contains an entry for this variant (Variation ID: 265111). 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: "Benign"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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