Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000690665 | SCV000818364 | uncertain significance | Charcot-Marie-Tooth disease type 4 | 2019-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with histidine at codon 261 of the SBF2 protein (p.Gln261His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs759932929, ExAC 0.04%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with SBF2-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: "Tolerated"; 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. |