Brief communicationNF2-related schwannomatosis (NF2-SWN) (NF2; MIM # 101000) is a neurogenetic condition caused by germline pathogenic variants in the NF2 gene. Affected individuals are predisposed to develop multiple tumours of the nervous system, particularly schwannomas, meningiomas and/or ependymomas.1 Bilateral vestibular schwannomas are a hallmark feature of NF2-SWN and can cause profound hearing loss. While most NF2-SWN variants are truncating variants that are relatively simple to classify as pathogenic, missense variants are less common and are generally more difficult to classify. Here, we refute the pathogenicity of two NF2 missense variants historically reported as causing NF2-SWN.
The majority of pathogenic NF2 variants are truncating variants, resulting in a premature stop codon. These variants are predicted to cause a complete loss of protein and normally lead to a severe NF2-SWN phenotype,2 characterised by earlier age at onset and/or an increased risk of meningiomas.3 A smaller proportion…
