ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.317G>A (p.Arg106His)

gnomAD frequency: 0.00003  dbSNP: rs145039212
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458507 SCV000552944 uncertain significance Charcot-Marie-Tooth disease, type I 2023-03-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 106 of the MPZ protein (p.Arg106His). This variant is present in population databases (rs145039212, gnomAD 0.007%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 411670). 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. This variant disrupts the p.Arg106 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22222859). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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, London Health Sciences Centre RCV001174318 SCV001337451 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Ambry Genetics RCV002323749 SCV002610202 uncertain significance Inborn genetic diseases 2021-05-04 criteria provided, single submitter clinical testing The p.R106H variant (also known as c.317G>A), located in coding exon 3 of the MPZ gene, results from a G to A substitution at nucleotide position 317. The arginine at codon 106 is replaced by histidine, an amino acid with highly similar properties. 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.

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