Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000032612 | SCV000060828 | pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2011-09-04 | criteria provided, single submitter | clinical testing | The Arg156His variant in EDA has been reported in at least 18 individuals with X -linked hypohidrotic ectodermal dysplasia (Schneider 2001, Monreal 1998, Schneid er 2011, Vincent 2001, Zhao 2008). This variant was reported as de novo in at le ast 4 individuals with de novo disease and was reported in an individual with a family history of X-linked hypohidrotic ectodermal dysplasia (Schneider 2001, Vi ncent 2001). Furthermore, functional studies have shown that the change to Histi dine (His) at position 156 affects protein cleavage (Chen 2001, Elomaa 2001). In summary, this variant meets our criteria to be classified as pathogenic. |
| Gene |
RCV000255365 | SCV000321580 | pathogenic | not provided | 2022-07-27 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect due to a drastic reduction in the cleavage of ectodysplasin-A as compared to wild-type, preventing the generation of a soluble ectodysplasin-A ligand (Chen et al., 2001); Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26273176, 23744313, 26411740, 11416205, 27305980, 26345974, 18231121, 11295832, 11309369, 18076698, 9683615, 11279189, 11378824, 28981473, 21357618, 34426522, 32690319, 32176048, 31924237, 29220840, 31796081, 34863015, 25333067, 17686277, 26502894, 18666859) |
| Invitae | RCV000032612 | SCV000630027 | pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2024-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 156 of the EDA protein (p.Arg156His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypohidrotic ectodermal dysplasia (PMID: 9683615, 11279189, 11295832, 11416205, 18231121). In at least one individual the variant was observed to be de novo. This variant is also known as c.708G>A (p.R156H). ClinVar contains an entry for this variant (Variation ID: 11037). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects EDA function (PMID: 11416205). This variant disrupts the p.Arg156 amino acid residue in EDA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9683615, 11279189, 11416205). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV002490354 | SCV002781148 | pathogenic | Hypohidrotic X-linked ectodermal dysplasia; Tooth agenesis, selective, X-linked, 1 | 2021-10-21 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000032612 | SCV000056366 | pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2009-07-01 | no assertion criteria provided | literature only |