Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002240938 | SCV001374191 | pathogenic | Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Autosomal recessive hypohidrotic ectodermal dysplasia syndrome | 2021-10-18 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Gly405 amino acid residue in EDAR. Other variant(s) that disrupt this residue have been observed in individuals with EDAR-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. 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 EDAR protein function. ClinVar contains an entry for this variant (Variation ID: 934620). This missense change has been observed in individual(s) with hypohidrotic ectodermal dysplasia (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 405 of the EDAR protein (p.Gly405Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. |