Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000821159 | SCV000961906 | uncertain significance | Charcot-Marie-Tooth disease, axonal, type 2O | 2019-02-08 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 3553 of the DYNC1H1 protein (p.Leu3553Val). 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 not been reported in the literature in individuals with DYNC1H1-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 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. |
Molecular Genetics Laboratory, |
RCV001173998 | SCV001337118 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |