Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics Laboratory, |
RCV001173697 | SCV001336810 | likely pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Invitae | RCV001224917 | SCV001397144 | pathogenic | Charcot-Marie-Tooth disease, type I | 2019-07-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with phenylalanine at codon 63 of the MPZ protein (p.Ser63Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Charcot-Marie-Tooth disease and to be de novo in at least one individual (PMID: 8835320, 15050444, 17294201). ClinVar contains an entry for this variant (Variation ID: 14177). This variant has been reported to affect MPZ protein function (PMID: 20461396). This variant disrupts the p.Ser63 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7506095, 16495463, 20937820). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000015240 | SCV000035499 | pathogenic | Charcot-Marie-Tooth disease, demyelinating, type 1b | 1995-12-01 | no assertion criteria provided | literature only |