Physician-directed genetic screening to evaluate personal risk for medically actionable disorders: a large multi-center cohort study

Table 4 Stratification of findings by genes or variants

All findings	Number (%)
Individuals with reportable findings	1619 (15.5)
Yield after excluding biallelic HFE and SERPINA1 findings	1423 (13.6)
Yield after excluding F2 and F5 findings and genes in the row above	973 (9.3)
Yield after excluding MUTYH heterozygotes and genes in rows above	829 (7.9)
Yield after excluding CHEK2 p.Ile157Thr and p.Ser428Phe heterozygotes, NBN heterozygotes (except for the NBN c.657_661delACAAA variant), and genes in rows above	746 (7.1)
Yield after excluding increased risk alleles (APC p.I1307K, HOXB13 p.Gly84Glu) and genes or variants in rows above	649 (6.2)
Findings in 59 genes prescribed by the ACMG
Individuals with reportable findings in the 59 ACMG genes	542 (5.2)
Yield after excluding MUTYH heterozygotes and increased risk alleles	326 (3.1)
Findings in CDC Tier 1 genes
All reportable findings in genes associated with HBOC, FH, and Lynch syndrome	205 (2.0)
HBOC findings only	114 (1.1)
Lynch syndrome findings only	51 (0.5)
FH findings only	41 (0.4)

ACMG American College of Medical Genetics and Genomics, CDC Centers for Disease Control and Prevention, HBOC hereditary breast and ovarian cancer, FH familial hypercholesterolemia
Stratification of results in the 59 genes prescribed by the ACMG is done by incrementally removing specific categories of gene groups (shown in successive rows) that are excluded per ACMG secondary findings guidelines. Similarly, stratification of results from CDC Tier 1 genes is shown based on different disease categories: HBOC syndrome (BRCA1 and BRCA2), Lynch syndrome (EPCAM, MLH1, MSH2, MSH6, and PMS2), and FH (APOB gain-of-function variants, LDLR, and PCSK9)

ISSN: 1741-7015