Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000518403 | SCV000614107 | likely pathogenic | not provided | 2020-08-26 | criteria provided, single submitter | clinical testing | This variant has been identified in at least one individual with clinical features associated with this gene. In our internal patient population, this variant is statistically more frequent than in the general population, which is weak evidence this variant may be disease causing (http://gnomad.broadinstitute.org). This variant occurs as the most likely explanation for disease in a significant number of internal cases, suggesting this variant is associated with disease. The variant is located in a region that is considered important for protein function and/or structure |
Invitae | RCV000638162 | SCV000759648 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 129 of the MPZ protein (p.Val129Ile). This variant is present in population databases (rs201156403, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MPZ-related conditions. ClinVar contains an entry for this variant (Variation ID: 447729). 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. |
Ambry Genetics | RCV002358399 | SCV002619979 | uncertain significance | Inborn genetic diseases | 2021-02-12 | criteria provided, single submitter | clinical testing | The p.V129I variant (also known as c.385G>A), located in coding exon 3 of the MPZ gene, results from a G to A substitution at nucleotide position 385. The valine at codon 129 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |