Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000690311 | SCV000817993 | uncertain significance | Hypohidrotic X-linked ectodermal dysplasia | 2018-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with glutamine at codon 56 of the EDA protein (p.Leu56Gln). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with EDA-related disease. ClinVar contains an entry for this variant (Variation ID: 569631). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. The p.Leu56 amino acid residue in EDA has been determined to be clinically significant (PMID: 25626993). This suggests that variants that disrupt this residue are likely to be causative of disease. 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. |