Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001068348 | SCV001233455 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate F | 2019-04-01 | criteria provided, single submitter | clinical testing | 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. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This variant has not been reported in the literature in individuals with GNB4-related conditions. This variant is present in population databases (rs776836938, ExAC 0.003%). This sequence change replaces threonine with serine at codon 198 of the GNB4 protein (p.Thr198Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. |
| Ambry Genetics | RCV002355093 | SCV002650404 | likely benign | Inborn genetic diseases | 2019-11-27 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |