Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000533146 | SCV000651653 | uncertain significance | Charcot-Marie-Tooth disease, axonal, type 2O | 2017-02-07 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 1765 of the DYNC1H1 protein (p.Ala1765Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs144147463, ExAC 0.008%) but has not been reported in the literature in individuals with a 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |