Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000516482 | SCV000614191 | uncertain significance | not specified | 2017-07-18 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000809657 | SCV000949822 | uncertain significance | Charcot-Marie-Tooth disease type 2E | 2018-09-10 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with aspartic acid at codon 265 of the NEFL protein (p.Tyr265Asp). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NEFL-related disease. ClinVar contains an entry for this variant (Variation ID: 447763). 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. |