Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000015238 | SCV000255799 | pathogenic | Charcot-Marie-Tooth disease type 1B | 2013-11-06 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000237048 | SCV000292963 | pathogenic | not provided | 2022-06-06 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect; R98C results in reduced transport of the MPZ protein to the plasma membrane (Lee et al., 2010; Saporta et al., 2012).; Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 12477701, 23250879, 9168174, 9187667, 20461396, 19293842, 8816708, 8797476, 17172621, 10093067, 8644725, 21840889, 28704293, 29687021, 15050444, 10207934, 31211173, 31827005, 33825325, 26310628, 24077912, 22689911) |
Invitae | RCV000548074 | SCV000636242 | pathogenic | Charcot-Marie-Tooth disease, type I | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 98 of the MPZ protein (p.Arg98Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease and Dejerine-Sottas syndrome (PMID: 8644725, 8797476, 9168174, 20461396, 21840889). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 14175). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MPZ protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects MPZ function (PMID: 20461396, 22689911). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000015238 | SCV001521544 | pathogenic | Charcot-Marie-Tooth disease type 1B | 2020-05-21 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV000015238 | SCV003807071 | pathogenic | Charcot-Marie-Tooth disease type 1B | 2022-06-05 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS3 supporting, PS4 strong, PM2 moderated, PM5 moderated, PM6 strong, PP3 supporting |
Ce |
RCV000237048 | SCV004704293 | pathogenic | not provided | 2024-02-01 | criteria provided, single submitter | clinical testing | MPZ: PS2, PM1, PM2, PM5, PS3:Supporting |
OMIM | RCV000015238 | SCV000035497 | pathogenic | Charcot-Marie-Tooth disease type 1B | 1996-03-01 | no assertion criteria provided | literature only |