Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000559816 | SCV000639668 | uncertain significance | Charcot-Marie-Tooth disease type 2E | 2017-05-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with glutamic acid at codon 328 of the NEFL protein (p.Ala328Glu). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and glutamine. This variant is present in population databases (rs768190580, ExAC 0.006%). This variant 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on NEFL function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |