Targeted Genomic Sequencing of TSC1 and TSC2 Reveals Causal Variants in Individuals for Whom Previous Genetic Testing for Tuberous Sclerosis Complex Was Normal
Table 1
Inactivating, likely germ-line TSC1 and TSC2 variants identified using HaloPlex custom capture NGS. Individuals fulfilling the clinical criteria for definite TSC [3] are indicated with “TSC”; those fulfilling only criteria for possible TSC are indicated with “?”; individuals for whom clinical information was not available to us are indicated with “n/a.” VAF, variant allele frequency, refers to the proportion of reads containing the corresponding variant. Cases for which multiple family members or multiple DNA samples were tested are indicated. Evidence for effects on pre-mRNA splicing was obtained by analysis of subject RNA isolated from either peripheral blood (RNA1.) or cultured skin fibroblasts (RNA2.). For functional studies please refer to the TSC1 and TSC2 Leiden Open Variation Databases (LOVD)(www.lovd.nl/TSC1, www.lovd.nl/TSC2). ClinVar (pathogenic, unless stated otherwise), the LOVD, and gnomAD, were accessed on 13/2/2023. P: pathogenic; LP: likely pathogenic; VUS: variant of uncertain clinical significance; LB: likely benign. Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) criteria [15] using the ALAMUT Visual Plus (version 1.7) software package.
