Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000546073 | SCV000657914 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2017-06-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 843 of the SH3TC2 protein (p.Gly843Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual who underwent genetic testing for Charcot-Marie-Tooth disease (PMID: 25614874). 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 create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on SH3TC2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Fulgent Genetics, |
RCV000765820 | SCV000897213 | uncertain significance | Charcot-Marie-Tooth disease, type 4C; Mononeuropathy of the median nerve, mild | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Molecular Genetics Laboratory, |
RCV001173153 | SCV001336230 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |