Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000691399 | SCV000819176 | uncertain significance | Charcot-Marie-Tooth disease, type 2L | 2018-02-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 55 of the HSPB8 protein (p.Arg55His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs752911264, ExAC 0.002%). This variant has not been reported in the literature in individuals with HSPB8-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. |