ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.309G>T (p.Gly103=) (rs1131691852)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493821 SCV000583003 likely pathogenic not provided 2017-05-18 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the MPZ gene. The c.309 G>T variant has been reported previously in multiple individuals with mild sensory-motor neuropathy from two unrelated families (Corrado et al., 2016). The c. 309G>T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.309 G>T creates a cryptic donor site which may supplant the natural donor site and lead to abnormal gene splicing. Functional studies suggest the c.309 G>T variant results in an increase of an alternative MPZ transcript (Corrado et al., 2016). However, this variant occurs at a position that is not conserved. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV001042393 SCV001206071 likely pathogenic Charcot-Marie-Tooth disease, type I 2019-03-20 criteria provided, single submitter clinical testing This sequence change affects codon 103 of the MPZ mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MPZ protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with mild demyelinating sensory-motor CMT polyneuropathy and has been shown to segregate with disease in a family (PMID: 27344971). ClinVar contains an entry for this variant (Variation ID: 430241). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 27344971). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.