Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001248236 | SCV001421706 | likely pathogenic | Charcot-Marie-Tooth disease, type 2 | 2020-02-05 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 248 of the MFN2 protein (p.Leu248Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 21508331, Invitae). It has also been observed to segregate with disease in related individuals. 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 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. |
| Inherited Neuropathy Consortium | RCV000789703 | SCV000929079 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |