Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000814912 | SCV000955350 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2018-12-05 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Asp121 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been observed in individuals with MPZ-related conditions (PMID:27774063), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MPZ-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 121 of the MPZ protein (p.Asp121Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. |
| CMT Laboratory, |
RCV001353168 | SCV001548329 | uncertain significance | Charcot-Marie-Tooth disease type 1B | 2020-12-01 | criteria provided, single submitter | clinical testing | |
| Genesis Genome Database | RCV000814912 | SCV000999691 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2019-08-14 | no assertion criteria provided | research |