Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000705857 | SCV000834874 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 183 of the MPZ protein (p.Trp183Arg). This variant is present in population databases (rs753107323, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 581905). 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%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Molecular Genetics Laboratory, |
RCV001174321 | SCV001337456 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Mayo Clinic Laboratories, |
RCV001508016 | SCV001713907 | uncertain significance | not provided | 2021-02-25 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002343564 | SCV002649861 | uncertain significance | Inborn genetic diseases | 2022-08-24 | criteria provided, single submitter | clinical testing | The p.W183R variant (also known as c.547T>C), located in coding exon 4 of the MPZ gene, results from a T to C substitution at nucleotide position 547. The tryptophan at codon 183 is replaced by arginine, an amino acid with dissimilar properties. This variant was identified in one allele in a Charcot-Marie Tooth cohort (Volodarsky M et al. J Med Genet, 2021 04;58:284-288). This amino acid position is highly 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. |