Submissions for variant NM_201384.3(PLEC):c.9295G>T (p.Glu3099Ter)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV005214938	SCV005858085	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	2024-02-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu3126*) in the PLEC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1449 amino acid(s) of the PLEC protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant disrupts a region of the PLEC protein in which other variant(s) (p.Lys4460*) have been determined to be pathogenic (PMID: 10652002). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.