Table 2 New gene–phenotype pairs for secondary findings (SF) list.
Gene–phenotype | Key considerations |
|---|---|
Genes related to cancer phenotypes | |
MAX/hereditary paraganglioma/pheochromocytoma | Penetrance met threshold to include with other PGL/PCC genes |
PALB2/hereditary breast cancer | Risk of breast cancer risk meets penetrance threshold |
TMEM127/hereditary paraganglioma/pheochromocytoma | Penetrance met threshold to include with other PGL/PCC genes |
Genes related to cardiovascular phenotypes | |
CASQ2/catecholaminergic polymorphic ventricular tachycardia (CPVT) | Risk of sudden death with preventive interventions available |
FLNC/cardiomyopathy | Risk of sudden death with preventive interventions available |
TRDN/catecholaminergic polymorphic ventricular tachycardia (CPVT) & long QT syndrome | Risk of sudden death with preventive interventions available |
TTN/cardiomyopathy | Risk of sudden death with preventive interventions available |
Genes related to inborn errors of metabolism phenotypes | |
BTD/biotinidase deficiency | Features can be nonspecific; highly effective treatment in children and adults |
GAA/Pompe disease | Availability of effective enzyme replacement therapy in infantile and later-onset cases |
Genes related to miscellaneous phenotypes | |
ACVRL1/hereditary hemorrhagic telangiectasia | Potential morbidity meets penetrance threshold and has efficacious intervention |
ENG/hereditary hemorrhagic telangiectasia | Potential morbidity meets penetrance threshold and has efficacious intervention |
HFE/hereditary hemochromatosis (HFE p.C282Y homozygotes only) | Potential morbidity meets penetrance threshold and has efficacious intervention |
HNF1A/maturity-onset diabetes of the young (MODY3) | Accounts for 30–50% of known MODY cases likely to respond to low dose sulfonylureas; early treatment may prevent complications |
RPE65/RPE65-related retinopathy | Availability of gene therapy treatment that may be more efficacious earlier in disease progression |
