Patients and control cohort
A total of 2,346 HC suspected patients were screened in two phases,
first 516 cases were screened for c.1100delC, exon 9-10 deletion and
c.470T>C recurrent variants and after 1,848 HC patients and
194 healthy controls were analyzed by mutligene panel testing (see
Figure 1 and Supplementary Material). Additionally, 1,501 control
samples were genotyped for the c.320-5T>A variant. Written
informed consent was obtained from all patients and the study protocol
was approved by the Ethics Committee of IDIBELL (PR278/19).
CHEK2 variant annotation and collection of variant
information. Variant annotation was performed using NM_007194.3 forCHEK2 gene (coding region and +/-20bp of intronic region). All
variants identified were submitted to Alamut Software Suite v2.15.0
(Interactive Biosoftware, Rouen, France) to retrieve population
frequency and in silico prediction data. Variant classification
in ClinVar as well as literature review were collected.