Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001337468 | SCV001531071 | likely 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 is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 405 of the EDAR protein (p.Gly405Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant has not been reported in the literature in individuals affected with EDAR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1034708). 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. This variant disrupts the p.Gly405 amino acid residue in EDAR. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |