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PURPOSE: The Clinical Genome Resource (ClinGen) Von Hippel-Lindau (VHL) Variant Curation Expert Panel (VCEP) has created variant classification specifications tailored to the VHL gene, including phenotype-driven and evidence-based criteria, utilizing somatic and germline mutational hotspots, along with functional and in-silico data.METHODS: Using the American College of Medical Genetics and Genomics (ACMG) guidance and the ClinGen Sequence Variant Interpretation (SVI) recommendations, the VCEP made substantial modifications to 8 evidence codes (PVS1, PS3, PS4, PM1, BS2, BS3, BS4, BP5), while 14 had minor changes, and 6 were not used (PM3, PP2, BP1, PP4, PP5/BP6). The VHL VCEP applied two literature sets of over >428 papers in Clinical Interpretations of Variants in Cancer (CIViC) and >8700 structured annotations using Hypothesis.RESULTS: From 31 pilot variants, 15 remained pathogenic/likely pathogenic, 9 resolved to benign through the stand-alone benign evidence code while 7 variants with initial uncertain classifications lacking additional evidence, remained uncertain.CONCLUSION: The versioned VHL VCEP specifications are publicly available in the ClinGen Criteria Specifications Registry and will enhance the transparency and consistency of variant classifications for this highly sequenced hereditary cancer gene.