Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000823331 | SCV000964185 | uncertain significance | Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C | 2021-04-08 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 435 of the PLEKHG5 protein (p.Tyr435Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PLEKHG5-related disease. This variant is not present in population databases (ExAC no frequency). |