Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001061577 | SCV001226325 | pathogenic | Charcot-Marie-Tooth disease, type I | 2023-11-04 | 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 106 of the MPZ protein (p.Arg106Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 22222859). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 637797). 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 not expected to disrupt MPZ protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002325494 | SCV002609598 | uncertain significance | Inborn genetic diseases | 2022-03-01 | criteria provided, single submitter | clinical testing | The p.R106C variant (also known as c.316C>T), located in coding exon 3 of the MPZ gene, results from a C to T substitution at nucleotide position 316. The arginine at codon 106 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was found in multiple individuals with late onset axonal motor and sensory polyneuropathy in the same family, as well as in one unrelated individual (Marttila M et al. J Neurol, 2012 Aug;259:1585-9). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Inherited Neuropathy Consortium | RCV000790114 | SCV000929504 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |