Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002025813 | SCV002287994 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 10 | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 3 of the DOK7 protein (p.Glu3Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs763233743, ExAC 0.01%). This missense change has been observed in individual(s) with clinical features of congenital myasthenic syndrome (PMID: 22661499; Invitae). 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 tolerated. Experimental studies have shown that this missense change affects DOK7 function (PMID: 22661499). 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. |