Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000799870 | SCV000939552 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2018-07-13 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with methionine at codon 62 of the MPZ protein (p.Ile62Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is present in population databases (rs121913605, ExAC 0.003%). This variant has been observed in an individual affected with Charcot-Marie-Tooth disease (PMID: 14638973). ClinVar contains an entry for this variant (Variation ID: 14194). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Variants that disrupt the p.Ile62 amino acid residue in MPZ have been observed in affected individuals (PMID: 10214757, 11935267). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. 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. |
| OMIM | RCV000015258 | SCV000035517 | pathogenic | Charcot-Marie-Tooth disease type 2I | 2003-11-25 | no assertion criteria provided | literature only |