Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000535604 | SCV000632649 | uncertain significance | GNE myopathy; Sialuria | 2016-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 700 of the GNE protein (p.Gly700Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs776384541, ExAC 0.02%). This variant has been reported in an individual affected with hereditary inclusion body myopathy (PMID: 23437777). This variant is also known as p.Gly669Arg in the literature. A different variant (c.2098G>C aka c.2005G>C) giving rise to the same protein effect observed here (p.Gly700Arg) has been reported in a patient affected with myopathy (PMID: 24027297), indicating that this residue may be critical for protein function. 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 C15"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and an affected individual, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| EGL Genetic Diagnostics, |
RCV000593273 | SCV000701430 | uncertain significance | not provided | 2017-05-23 | criteria provided, single submitter | clinical testing |