Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001874086 | SCV002119381 | uncertain significance | Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant; Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive | 2021-05-17 | criteria provided, single submitter | clinical testing | 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. 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). This variant has been observed in individual(s) with autosomal dominant ectodermal dysplasia (Invitae). The frequency data for this variant in the population databases is not available, as this variant may be reported as separate entries in the ExAC database. This sequence change replaces aspartic acid with isoleucine at codon 120 of the EDARADD protein (p.Asp120Ile). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and isoleucine. This variant disrupts the p.Asp120 amino acid residue in EDARADD. Other variant(s) that disrupt this residue have been observed in individuals with EDARADD-related conditions (PMID: 20979233), which suggests that this may be a clinically significant amino acid residue. 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. |