Most MPT-affected individuals (38/67 [56.7%] and 38/440 [8.6%] of all pre-assessed probands tested in the current study) with a P/LP variant had been diagnosed with a tumor type characteristically associated with variants in the relevant CPG, findings that have the greatest clinical utility. In, addition, a further 8/440 (1.8%) had a VUS and a previous diagnosis of a characteristic tumor. Such VUSs might eventually be reclassified as LP variants with further investigations (e.g., tumor studies or functional analysis) or additional clinical information (e.g., segregation analysis). However, interpretation of segregation data should be cautious in cancer-predisposition syndromes because of incomplete penetrance and a higher probability of phenocopies. Tumor studies for loss of heterozygosity do not provide absolute confirmation or exclusion of pathogenicity, and together these considerations reinforce the importance of data-sharing initiatives such as ClinVar.20