Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001385506 | SCV001585384 | pathogenic | Charcot-Marie-Tooth disease, type I | 2020-08-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asn131 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10553995, 12940837). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 20621479, 21940171, Invitae). ClinVar contains an entry for this variant (Variation ID: 637784). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 131 of the MPZ protein (p.Asn131Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. |
| Inherited Neuropathy Consortium | RCV000790100 | SCV000929490 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |