INCIDENTAL FINDINGS

By sequencing all genes (exome/genome sequencing) we might also find disease-causing mutations in genes unrelated to the phenotype in question, but which may cause severe health problems (e.g. mutations causing susceptibility to cancer or certain heart diseases). These are called incidental findings (or secondary findings). For example, we might find a breast cancer-predisposing mutation in a patient tested for thoracic aortic aneurysm (e.g. a BRCA1 mutation). In such a case, if the patient has previously given consent, the breast-cancer mutation will also be reported. Incidental findings come as ADD-ON for EXOME GENE and EXOME PANEL, whereas they are included in EXOME 15MB, EXOME 33MB, EXOME 50MB, and GENOME FULL. However, it is good to highlight that the likelihood of generating incidental findings is relatively low: an incidental finding can be found in 1-3% of all tests in average. It should be reminded that, when an incidental finding is found in a child, this has been most likely inherited from one of the parents, so incidental findings detection can be of clinical relevance also for the father, the mother and the siblings.

The American College of Medical Genetics has issued a list of genes for which incidental findings should be reported. As of 30.04.2015, this list includes the following genes:

Condition
Typical Age of Onset
Gene
Inheritance
Hereditary breast and ovarian cancer
Adult
BRCA1
BRCA2
Autosomal dominant
Li–Fraumeni syndrome
Child/adult
TP53
Autosomal dominant
Peutz–Jeghers syndrome
Child/adult
STK11
Autosomal dominant
Lynch syndrome
Adult
MLH1
MSH2
MSH6
PMS2
Autosomal dominant
Familial adenomatous polyposis
Child/adult
APC
Autosomal dominant
MYH-associated polyposis; adenomas, multiple colorectal, FAP type 2; colorectal adenomatous polyposis, autosomal recessive, with pilomatricomas
Adult
MUTYH
Autosomal recessive
Von Hippel–Lindau syndrome
Child/adult
VHL
Autosomal dominant
Multiple endocrine neoplasia type 1
Child/adult
MEN1
Autosomal dominant
Multiple endocrine neoplasia type 2
Child/adult
RET
Autosomal dominant
Familial medullary thyroid cancer
Child/adult
RET
Autosomal dominant
PTEN hamartoma tumor syndrome
Child/adult
PTEN
Autosomal dominant
Retinoblastoma
Child
RB1
Autosomal dominant
Hereditary paraganglioma– pheochromocytoma syndrome
Child/adult
SDHD
SDHAF2
SDHC
SDHB
Autosomal dominant
Tuberous sclerosis complex
Child
TSC1
TSC2
Autosomal dominant
WT1-related Wilms tumor
Child
WT1
Autosomal dominant
Neurofibromatosis type 2
Child/adult
NF2
Autosomal dominant
Ehlers–Danlos syndrome, vascular type 1
Child/adult
COL3A1
Autosomal dominant
Marfan syndrome, Loeys–Dietz syndromes, and familial thoracic aortic aneurysms and dissections
Child/adult
FBN1
TGFBR1
TGFBR2
SMAD3
ACTA2
MYLK
MYH11
Autosomal dominant
Hypertrophic cardiomyopathy, dilated cardiomyopathy
Child/adult
MYBPC3
MYH7
TNNT2
TNNI3
TPM1
MYL3
ACTC1
PRKAG2
GLA
MYL2
LMNA
Autosomal dominant / X-linked
Catecholaminergic polymorphic ventricular tachycardia
RYR2
Autosomal dominant
Arrhythmogenic right-ventricular cardiomyopathy
Child/adult
PKP2
DSP
DSC2
TMEM43
DSG2
Autosomal dominant
Romano–Ward long QT syndrome types 1, 2, and 3, Brugada syndrome
Child/adult
KCNQ1
KCNH2
SCN5A
Autosomal dominant
Familial hypercholesterolemia
Child/adult
LDLR
APOB
PCSK9
Autosomal dominant / Semidominant
Malignant hyperthermia susceptibility
Child/adult
RYR1
CACNA1S
Autosomal dominant