Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003794742 | SCV004587461 | uncertain significance | 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 | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change affects codon 448 of the PLEC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PLEC protein. This variant also falls at the last nucleotide of exon 13, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |