ClinVar Miner

Submissions for variant NM_000304.4(PMP22):c.215C>G (p.Ser72Trp) (rs104894621)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000802360 SCV000942186 likely pathogenic Charcot-Marie-Tooth disease, type I 2018-08-15 criteria provided, single submitter clinical testing This sequence change replaces serine with tryptophan at codon 72 of the PMP22 protein (p.Ser72Trp). The serine residue is highly conserved and there is a large physicochemical difference between serine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with Dejerine–Sottas disease (PMID: 9055797). 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. Variants that disrupt the p.Ser72 amino acid residue in PMP22 have been observed in affected individuals (PMID: 8275092, 9004143, 9585367, 10399754, 11314784). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. 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.
GeneDx RCV001580546 SCV001817890 likely pathogenic not provided 2020-03-03 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported previously in a mother and son with Dejerine-Sottas disease (Tyson et al., 1997).; This variant is associated with the following publications: (PMID: 28374912, 23224996, 9055797)
Inherited Neuropathy Consortium RCV000790174 SCV000929565 uncertain significance Dejerine-Sottas disease no assertion criteria provided literature only

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.