Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001903357 | SCV002160058 | uncertain significance | Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Autosomal recessive hypohidrotic ectodermal dysplasia syndrome | 2021-07-26 | criteria provided, single submitter | clinical testing | 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Cys47 amino acid residue in EDAR. Other variant(s) that disrupt this residue have been observed in individuals with EDAR-related conditions (PMID: 16435307), which suggests that this may be a clinically significant amino acid residue. This variant has been observed in individual(s) with clinical features of ectodermal dysplasia (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tryptophan at codon 47 of the EDAR protein (p.Cys47Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. |