Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000530689 | SCV000639666 | uncertain significance | Charcot-Marie-Tooth disease type 2E | 2017-05-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamate with glycine at codon 266 of the NEFL protein (p.Glu266Gly). The glutamate residue is highly conserved and there is a moderate physicochemical difference between glutamate and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a NEFL-related disease. 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. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |