Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000641077 | SCV000762695 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2F | 2019-10-19 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with asparagine at codon 123 of the HSPB1 protein (p.Lys123Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs755233365, ExAC 0.002%). This variant has not been reported in the literature in individuals with HSPB1-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: "Probably 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. |