Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001350133 | SCV001544512 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2025-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 30 of the MPZ protein (p.Ile30Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease and/or MPZ-related conditions (PMID: 25614874; internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1045680). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MPZ protein function with a negative predictive value of 80%. This variant disrupts the p.Ile30 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7694726, 17143884, 20461396, 26454100). 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. |
| Athena Diagnostics | RCV002473277 | SCV002771872 | likely pathogenic | not provided | 2021-06-28 | criteria provided, single submitter | clinical testing | This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic, suggesting this variant may also cause disease. The variant is located in a region that is considered important for protein function and/or structure. Computational tools predict that this variant is damaging. |
| Ambry Genetics | RCV004036610 | SCV004994393 | uncertain significance | Inborn genetic diseases | 2023-10-27 | criteria provided, single submitter | clinical testing | The c.88A>G (p.I30V) alteration is located in exon 2 (coding exon 2) of the MPZ gene. This alteration results from a A to G substitution at nucleotide position 88, causing the isoleucine (I) at amino acid position 30 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |