Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000528090 | SCV000649210 | uncertain significance | Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2017-08-08 | criteria provided, single submitter | clinical testing | 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: "Benign"; Align-GVGD: "Class C0"). This variant is present in population databases (rs775185806, ExAC 0.001%) but has not been reported in the literature in individuals with a SYNE1-related disease. This sequence change replaces aspartic acid with asparagine at codon 2652 of the SYNE1 protein (p.Asp2652Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |