Table 3 Summary of PPV and clinical actionability for genes with significant associations and PPV ≥0.3 in our study.

From: Positive predictive value highlights four novel candidates for actionable genetic screening from analysis of 220,000 clinicogenomic records

Condition	Hereditary breast and ovarian cancer^a		Type 2 diabetes^a	Gestational diabetes	β-thalassemia minor and intermedia^b	Familial hypercholesterolemia^a	Cataracts	Chronic kidney disease
Associated complications	Breast, ovarian, prostate, and pancreatic cancers and melanoma		Microvascular disorders	Macrosomia	Anemia, osteoporosis, iron overload	Atherosclerotic cardiovascular disease	Blurry vision up to blindness	Early onset hypertension, cyst infections
Nongenetic surveillance available to confirm or monitor disease?	Mammograms, MRIs, transvaginal ultrasound, regular CA-125 surveillance, PSA surveillance		Glucose and HbA1C surveillance	OGTT	CBC with smear, hemoglobin analysis	Lipid blood tests	Slit lamp eye exam	TKV, serum creatinine, eGFR
Treatment options (to mitigate, prevent, or reverse)	Risk-reducing surgeries		Diet, exercise, metformin, other oral hypoglycemic agents, insulin	Diet change and intense monitoring; insulin needed if diet and exercise do not help	Supplementation, blood transfusion, iron chelation	Statins. May also consider ezetimibe, bile acid sequestrants, niacin, PCSK9 inhibitors, LDL apheresis	Cataract surgery	Various drug options to slow progression
Associated gene	BRCA1	BRCA2	GCK		HBB	LDLR	MIP	PKD1
% with variant^c	0.11%	0.36%	0.06%		0.06%^c	0.03%	0.06%	0.03%
PPV^c	0.43	0.35	0.5	0.82^e	0.59	0.5	0.43	0.44
Diagnose earlier with genetic screening, and cascade test?	Yes	Yes	Yes	Yes	Yes^f	Yes	Yes	Yes
How are genetic cases treated differently?	Earlier monitoring/treatment	Earlier monitoring/treatment	GCK forms usually need no interventions [22]	Tailor treatment based on genotype of fetus	Usually do not give iron for anemia; reproductive counseling	Earlier monitoring/treatment	Earlier monitoring/treatment	Screen TKV to track disease progression [26]

CBC complete blood count, eGFR estimated glomerular filtration rate, MRI magnetic resonance image, OGTT oral glucose tolerance test, PPV positive predictive value, TKV total kidney volume.
^aConditions already part of existing population screening programs and part of CDC Tier 1.
^bComplications and treatments differ depending on the exact type of β-thalassemia, with β-thalassemia minor having no complications beyond mild anemia.
^cFrequency varies substantially by population.
^dCalculated for the significant phenotype and model with the highest PPV for this gene in this study.
^eWhen controls are restricted to pregnant females.
^fWhile symptomatic thalassemia is generally diagnosed in childhood, 71% of the heterozygotes in the present study were diagnosed as adults.

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Table 3 Summary of PPV and clinical actionability for genes with significant associations and PPV ≥0.3 in our study.

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