Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000037181 | SCV000060838 | likely pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2012-05-18 | criteria provided, single submitter | clinical testing | The Pro203Ser variant in EDA has not been reported in the literature nor previou sly identified by our laboratory. Computational analyses (biochemical amino aci d properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that this va riant may impact the protein, though this information is not predictive enough t o determine pathogenicity. Other mutations affecting nearby residues and also af fecting nearby proline residues have been associated to EDA increasing the likel ihood that this mutation is pathogenic. Furthermore, the presence of this mutati on in a patient with features of hypohidrotic ectodermal dysplasia and an X-link ed family history further supports the likelihood that this variant is pathogeni c. In summary, although additional data is needed to fully assess its clinical s ignificance, this variant is more likely pathogenic. |
Invitae | RCV000037181 | SCV001542496 | likely pathogenic | Hypohidrotic X-linked ectodermal dysplasia | 2022-12-20 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Pro203 amino acid residue in EDA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27305980; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 44203). This variant has not been reported in the literature in individuals affected with EDA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 203 of the EDA protein (p.Pro203Ser). |