ClinVar Miner

Submissions for variant NM_201631.4(TGM5):c.763T>C (p.Trp255Arg) (rs115677373)

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
Illumina Clinical Services Laboratory,Illumina RCV000144912 SCV000914675 pathogenic Peeling skin syndrome 2 2019-01-11 criteria provided, single submitter clinical testing The TGM5 c.763T>C (p.Trp255Arg) missense variant has been reported in at least three studies in which it is found in a compound heterozygous state in a total of eight individuals, including two siblings, all affected with peeling skin syndrome, and in each case, in trans with the most common pathogenic variant (p.Gly113Cys) (Kiritsi et al. 2010; Szczecinska et al. 2014; Has et al. 2018) . The p.Trp255Arg variant was absent from 100 control chromosomes and is reported at a frequency of 0.000795 in the European (non-Finnish) population of the Exome Aggregation Consortium. The Trp255 residue is highly conserved. Functional studies by Kiritsi et al. (2014) demonstrated that the variant protein was restricted to a few skin cell layers in contrast to the more extensive localisation of the wild type protein. Structural modelling showed that the Trp255 residue lies in the core domain close to the catalytic site and that the variant induces significant conformational and electrostatic changes within the protein. Based on the collective evidence, the p.Trp255Arg variant is classified as pathogenic for peeling skin syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000144912 SCV000191914 pathogenic Peeling skin syndrome 2 2010-06-01 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.