Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000559005 | SCV000639665 | likely pathogenic | Charcot-Marie-Tooth disease type 2E | 2017-06-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 266 of the NEFL protein (p.Glu266Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an NEFL-related disease. Family studies have indicated that this variant was not present in the parents of an individual with a progressive axonal/demyelinating polyneuropathy, which suggests that it was de novo in that affected individual (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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |