Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001778676 | SCV002015704 | pathogenic | not provided | 2021-11-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 9736768, 14656435, 30117778, 11378824, 25333067, 9683615, 20979233) |
Invitae | RCV000037191 | SCV002221809 | pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2023-08-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly299 amino acid residue in EDA. Other variant(s) that disrupt this residue have been observed in individuals with EDA-related conditions (PMID: 20236127, 21357618, 26273176, 26345974), which suggests that this may be a clinically significant amino acid residue. 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 expected to disrupt EDA protein function. ClinVar contains an entry for this variant (Variation ID: 44213). This missense change has been observed in individuals with ectodermal dysplasia (PMID: 9683615, 30117778). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 299 of the EDA protein (p.Gly299Ser). |
Laboratory for Molecular Medicine, |
RCV000037191 | SCV000060848 | likely pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2011-07-26 | no assertion criteria provided | clinical testing | The Gly299Ser variant in EDA has been reported in 3 individuals with X-linked hy pohidrotic ectodermal dysplasia and was absent in 135 control chromosomes (Bayes 1998, Monreal 1998). In addition, based on the crystal structure this variant i s predicted to affect the overall structure of EDA (Hymowitz 2003). Furthermore, this residue is conserved across species and computational analyses (PolyPhen2, SIFT, AlignGVGD) suggest that the Gly299Ser variant may impact the protein. In summary, this variant is likely to be pathogenic. |