ClinVar Miner

Submissions for variant NM_001399.5(EDA):c.871G>A (p.Gly291Arg) (rs397516677)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037189 SCV000060846 pathogenic Hypohidrotic X-linked ectodermal dysplasia 2011-09-17 criteria provided, single submitter clinical testing The Gly291Arg variant in EDA has been reported in at least 11 individuals with X -linked hypohidrotic ectodermal dysplasia. It was reported as de novo in two of these individuals and was absent from over 300 control chromosomes (Bayes 1998, Cluzeau 2011, Schneider 2001, Schneider 2011, Sekiguchi 2005, LMM unpublished d ata). In summary, this variant meets our criteria to be classified as pathogeni c.
GeneDx RCV000256153 SCV000321584 pathogenic not provided 2018-04-19 criteria provided, single submitter clinical testing The G291R pathogenic variant in the EDA gene has been reported previously in association with X-linked hypohidrotic ectodermal dysplasia (Bayes et al., 1998; Schneider et al., 2011; Cluzeau et al., 2011). The G291R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G291R 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 G291R as a pathogenic variant.
Invitae RCV000037189 SCV001220181 pathogenic Hypohidrotic X-linked ectodermal dysplasia 2020-01-02 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 291 of the EDA protein (p.Gly291Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hypohidrotic/anhidrotic ectodermal dysplasia (PMID: 9736768, 23553579, 22032522, 21357618, 20979233). This variant is also known as c.1113G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 44211). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.

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