Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001377519 | SCV001574874 | likely pathogenic | Charcot-Marie-Tooth disease, type I | 2020-03-10 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with serine at codon 30 of the MPZ protein (p.Ile30Ser). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and serine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ile30 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7694726, 20461396, 17143884). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 19259128, Invitae). ClinVar contains an entry for this variant (Variation ID: 637340). This variant is not present in population databases (ExAC no frequency). |
| Inherited Neuropathy Consortium | RCV000789461 | SCV000928817 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |