Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000201151 | SCV000255804 | pathogenic | Charcot-Marie-Tooth disease, demyelinating, type 1b | 2015-06-17 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000464045 | SCV000552942 | pathogenic | Charcot-Marie-Tooth disease, type I | 2018-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with methionine at codon 30 of the MPZ protein (p.Ile30Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Charcot-Marie-Tooth disease, type 1B and has been reported to segregate in affected families (PMID: 7694726, 26454100, Invitae database). ClinVar contains an entry for this variant (Variation ID: 217235). 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 C0"). Different missense substitution at this codon (p.Ile30Phe, p.Ile30Ser, p.Ile30Thr) have been identified in individuals affected with Dejerine–Sottas disease and Charcot-Marie-Tooth disease (PMID: 17143884, 19259128, 20461396). This suggests that the isoleucine residue may be critical for MPZ protein function. For these reasons, this variant has been classified as Pathogenic. |
| Athena Diagnostics Inc | RCV000712322 | SCV000842788 | pathogenic | not provided | 2015-06-17 | criteria provided, single submitter | clinical testing | |
| Inherited Neuropathy Consortium | RCV000789438 | SCV000928793 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |