Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000649584 | SCV000771413 | uncertain significance | Charcot-Marie-Tooth disease, axonal, type 2O | 2019-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with aspartic acid at codon 481 of the DYNC1H1 protein (p.Val481Asp). The valine residue is moderately conserved and there is a large physicochemical difference between valine and aspartic acid. This variant is present in population databases (rs776102509, ExAC 0.002%). 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |