Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000698448 | SCV000827113 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2019-03-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with glutamic acid at codon 310 of the SH3TC2 protein (p.Gly310Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is present in population databases (rs763949764, ExAC 0.02%). This variant has been observed in individuals affected with autosomal recessive Charcot-Marie-Tooth disease (PMID: 27025386, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 576051). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |