Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000648519 | SCV000770339 | likely pathogenic | Epidermolysis bullosa simplex 5B, with muscular dystrophy; Epidermolysis bullosa simplex, Ogna type; Epidermolysis bullosa simplex 5C, with pyloric atresia; Autosomal recessive limb-girdle muscular dystrophy type 2Q; Epidermolysis bullosa simplex with nail dystrophy | 2018-02-16 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the PLEC gene (p.Gln3811*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 763 amino acids of the PLEC protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PLEC-related disease. This truncation would remove the intermediate filament-binding domain from the resulting plectin protein.  This particular domain is important for the proper interaction between plectin and other cytoskeleton proteins (PMID: 8830774, 19945614). Several downstream variants, also resulting in a premature translational stop signal, have been identified in the compound heterozygous state with other pathogenic PLEC variants in individuals affected with epidermolysis bullosa (EB), which explains the cause for recessive disease in these individuals. Further, it suggests that truncations in this region of the protein, while not resulting in nonsense mediated decay, are likely to be pathogenic (PMID: 23289980, 10652002). 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. |