Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000638158 | SCV000759644 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2017-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 88 of the MPZ protein (p.Tyr88Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). A different missense substitution at this codon (p.Tyr88His) has been reported in an individual affected with Charcot-Marie-Tooth disease (PMID: 27025386). 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 C15"). 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. |