Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000555399 | SCV000630037 | pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 324 of the EDA protein (p.Val324Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of ectodermal dysplasia (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 458662). 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%. This variant disrupts the p.Val324 amino acid residue in EDA. Other variant(s) that disrupt this residue have been observed in individuals with EDA-related conditions (PMID: 23989902), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |