Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000144912 | SCV000914675 | pathogenic | Acral peeling skin syndrome | 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 | Acral peeling skin syndrome | 2010-06-01 | no assertion criteria provided | literature only |