ClinVar Miner

Submissions for variant NM_022336.4(EDAR):c.1135G>A (p.Glu379Lys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003806765 SCV004596878 likely pathogenic Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Autosomal recessive hypohidrotic ectodermal dysplasia syndrome 2023-09-03 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 379 of the EDAR protein (p.Glu379Lys). This variant is present in population databases (rs770369940, gnomAD 0.02%). This missense change has been observed in individuals with clinical features of autosomal dominant EDAR-related conditions (PMID: 23991204; Invitae). 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 EDAR protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on EDAR function (PMID: 10431242, 15013427). 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.
GeneDx RCV004719393 SCV005325739 uncertain significance not provided 2023-11-10 criteria provided, single submitter clinical testing Reported in individuals with tooth agenesis in the published literature (PMID: 23991204); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23991204)

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