Variant interpretation

Question 1

Genetic changes that may be missed in testing

Answer 1

• epigenetic alterations (abnormal methylation)
• trinucleotide repeat expansion
• deep intronic changes

Question 2

Li- Fraumeni syndrome

Answer 2

• autosomal dominant
• TP53
• The lifetime risk of cancer is ≥70% for men and ≥90% for women Risk changes with age. 22% of the cancers between 0 and 15 years, 51% between 16 and 50 years, and 27% between 51 and 80 years

Question 3

Phasing (testing parents)

Answer 3

Variants in cis or trans in AR disorder
De novo data gives moderate/strong evidence of pathogenicity