Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002234006 | SCV000760963 | uncertain significance | Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Autosomal recessive hypohidrotic ectodermal dysplasia syndrome | 2020-08-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 63 of the EDAR protein (p.Gly63Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant has not been reported in the literature in individuals with a EDAR-related disease. This variant is present in population databases (rs764223500, ExAC 0.01%). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; 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. 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. |