Download Comprehensive Genetic Testing

Comprehensive Genetic Testing
portfolio
overview
In this era of individualized and
precision medicine, you need
individualized test options.
Although the landscape of clinical genetics is changing
rapidly, Ambry brings almost two decades of experience
and commitment to excellence in testing, as well as a
longstanding dedication to innovation. We continue to be
a leader in diagnostic solutions by offering options that fit
to your patient: single genes testing, multi-gene panels
of varying sizes, reflex/tiered panels, and whole exome
sequencing.
Company-wide investments in quality support trustworthy
testing, like specialized scientists, technology, and human
resources.
Did You Know
Dramatic advances in DNA sequencing technology
have made large-scale genetic testing more affordable
and informative. These advances accelerate the rate
at which gene-disease associations are discovered,
which profoundly impacts clinical care: it increases
our ability to provide patients and families with a
meaningful genetic diagnosis.
Adapted from Farwell Hagman KD, et al., Genetics in Medicine,
2016.
Dovetailing with our testing are our services aimed to
make things easier and simpler for you and your patients,
such as insurance preverification, our "one sample, one
bill" concept, and robust genetic variant analysis.
One Size Does Not Fit All: Customizable Testing Options
CustomNext-Cancer
Analyzes up to 67 hereditary
cancer genes of your choice
CustomNext-TAAD
CustomNext-Cardio
Analyzes up to 85 cardiovascular
genes of your choice
Analyzes up to 22 genes of your choice associated with
thoracic aortic aneurysms and dissections, Marfan
syndrome, or related disorders
CustomNext-Epilepsy
Analyzes up to 100 epilepsy
genes of your choice
ExomeNext-Select
A testing option that includes whole exome
sequencing, with focused analysis on a pre-selected
list of genes based on your patient’s phenotype
table of contents
1 clinical genomics
Introduction
2 microarray analysis
SNP Array
3 exome sequencing
Highlights: ExomeNext, ExomeNext-Rapid, and ExomeNext-Select
5 multiple congenital anomalies
Highlights: Noonan syndrome, Cornelia de Lange syndrome,
and Prader-Willi syndrome
6 neurodevelopmental disorders
Highlights: Targeted panels for autism and intellectual disability,
our broad panel for neurodevelopmental disorders
7 epilepsy
Highlights: Phenotype-specific panels and our broad
panel for epilepsy
8 inherited metabolic disorders
Lysosomal storage disorders, Leukodystrophies
9 pulmonology
Highlights: Cystic fibrosis, Primary ciliary dyskinesia
10 vascular disorders
Highlights: Hereditary hemorrhagic telangiectasia,
Thoracic aortic aneurysms/dissections
11 cardiology
Highlights: Familial hypercholesterolemia, Thoracic aortic
aneurysms/dissections, Arrhythmias, Cardiomyopathies
13 gastroenterology
14 endocrinology
Highlights: Maturity-onset diabetes of the young, Multiple
endocrine neoplasia type 1, Hereditary paraganglioma/
pheochromocytoma
15 neurocutaneous/
neuro-oncology disorders
Highlights: Neurofibromatosis 1, Tuberous sclerosis complex,
Li-Fraumeni syndrome
16 pediatric oncology
Highlight: Hereditary retinoblastoma
17 hematology-oncology
Highlight: Diamond-Blackfan anemia
18 oncology
Highlight: Our 32-gene cancer susceptibility panel for at least 8
major cancers (including breast, colorectal, ovarian, and uterine)
19 test ordering
5 simple steps to order testing, Specimen requirements
21 variant assessment and classification
How we individualize our analysis of genetic variants
22 progeny
Overview of the powerful risk modeling and pedigree software
23 community outreach
Patient Websites, Mauli Ola Foundation, AmbryShare
24 about ambry
Support
Billing and Insurance: Excellent Coverage, Personalized Support
Highlight: Pancreatitis
*This page does not represent our complete genetic testing menu. For a more expanded look including testing methodologies and other testing options,
please visit ambrygen.com. Many genes included in panels may be ordered separately as single gene tests.
ambrygen.com
clinical genomics
1
clinical genomics
These powerful testing options have the goal of efficiently finding the underlying cause to
explain a constellation of medical concerns.
Many genetic disorders involve multiple body systems. Clinical genomics testing can identify a cause that explains all
medical symptoms, across the genome, in a timely manner. Genomic variation may be as small as single base changes
or as large as full chromosome variations spanning millions of bases. We offer testing covering numerous scales of
genomic variation. Clinical genomics testing options may be ordered by themselves, or in conjunction with single gene
testing or multi-gene panels.
Scale of Genomic Variation
chromosome
100 million bases
microarray
analysis
cnv
30,000 to 3 million bases
single gene
3 ,000 bases
A T C G C G C TTT A T A T C GG C A T A C G C A T G C T
sequence change
1 base
tct
exome
sequencing
m i c r o a r r ay a n a ly s i s
2
microarray analysis
Chromosomal Microarray Analysis (CMA)
Chromosomal microarray analysis (CMA) is a genome-wide
test designed to detect copy number variants (CNV), or
extra/missing regions, in the chromosomes.
CMA can find imbalances that even a high-resolution
karyotype analysis would miss, with a 5x greater diagnostic
yield over traditional chromosome analysis (15-20%
versus 3%) for patients with unexplained DD, ID, ASDs,
and/or MCA.1
In addition to its recommended use for the evaluation of
MCA, DD/ID and ASDs, emerging evidence suggests
CMA is a cost-effective approach for testing individuals
with other diagnoses including chronic kidney disease,
congenital heart defects, and infantile spasms.
American College of Medical Genetics and
Genomics (ACMG) Guideline
CMA is recommended as a first-tier genetic test in the
postnatal evaluation of individuals with MCA, DD/ID,
and ASDs. For patients with ASDs or DD/ID, fragile X
syndrome testing may be considered along with CMA.
Adapted from Miller DT, et al., Am J Hum Genet., 2010.
SNP Array
Our CMA test, SNP Array, is useful for the identification of CNVs, regions of homozygosity (ROH) and risk for uniparental
disomy (UPD). Single nucleotide polymorphism (SNP) probe coverage allows for:
• Detection of ROH*, which may indicate a risk for autosomal recessive disorders and may identify consanguinity
• Detection of risk for UPD, relevant to conditions like transient neonatal diabetes mellitus, Beckwith-Wiedemann
syndrome, Prader-Willi syndrome, Angelman syndrome, and Russell-Silver syndrome
SNP Array Highlights
Probe number
2.6 million copy number probes
750,000 SNP probes
Genome-wide detection of CNVs
x
Detection of ROH and risk for UPD
x
Median probe spacing
Turnaround time
1kb throughout the genome
14-21 days
*The 180K Oligo array option is also available at a lower price and shorter TAT of 10-14 days, but does not detect ROH.
1
Miller DT, et al., Am J Hum Genet., 2010.
ambrygen.com
exome
3
exome sequencing
e xome
Clinical Diagnostic Exome Sequencing
(ExomeNext)
Clinical diagnostic exome sequencing involves sequencing
all of the protein coding regions of all the genes of the
genome, in order to identify an underlying genetic cause for
a phenotype in question. Most mutations causing
Mendelian disorders are located within the exons.1 The
human exome (exons for the entire human genome) is only
1-2% percent of the entire genome.
g enome
Clinical Indications for Exome Sequencing
Diagnostic exome sequencing is rapidly becoming the standard of care for patients with rare diseases, as it offers a
one-step, unbiased interrogation of virtually all of the coding regions of the genome. Consider exome sequencing when:
• The suspected genetic condition has become a “diagnostic odyssey,” with no genetic explanation identified from
prior testing
• Limited or no comprehensive tests are available for the suspected condition
• Clinical presentation does not correspond with a known genetic disorder, but a candidate genetic etiology is suspected
• Clinical presentation is unclear/atypical and may involve multiple genes, making ExomeNext a more practical approach
• Available targeted genetic testing for a fetus with a likely genetic condition has failed to arrive at a diagnosis
ExomeNext
ExomeNext uses next generation methods to sequence the
exome. This, coupled with our powerful bioinformatics
pipeline, identifies a clinical answer efficiently and
effectively through analysis of all 20,000 genes of the
genome. Mitochondrial DNA (mtDNA) sequencing and
analysis are also performed and included in ExomeNext.
Analysis and reporting are based on the type of test
ordered. Co-segregation analysis of family members is
always included for candidate variants identified. Secondary
findings are included for the parents and family members
sequenced as part of the trio.
ExomeNext-Rapid is our fastest exome test, geared towards
babies in the NICU or other patients needing an immediate
diagnosis. We also offer ExomeNext-Prenatal, a diagnostic
test available for high-risk ongoing pregnancies.
1
Pussegoda KA, et al., Clin Genet., 2010.
ExomeNext-Select
ExomeNext-Select is a customizable exome test. You may
choose up to 500 genes to be reported based on your
patient's clinical presentation. This test utilizes NGS to
sequence the entire exome, which is coupled with our
powerful bioinformatics pipeline. Analysis is limited to
the genes selected for reporting. MtDNA sequencing is
not included in this test option.
exome
4
ExomeNext Options (not including ExomeNext-Prenatal)
exomenext
exomenext- rapid*
exomenext- select
8-12 weeks
8 days**
8-12 weeks
Up to ~20,000***
Up to ~20,000***
Up to 500
Included
Included
No
Trio
Trio
One
Family studies
Included
Included
Included
Secondary Findings Results
Included
Included
No
Turnaround time
Number of genes analyzed
Mitochondrial genome
Number of individuals sequenced
* Only institutional and cash billing are accepted
** Verbal result provided within 8 days; full report including mtDNA analysis, co-segregation analysis, and Sanger confirmation provided within 14 days.
*** Analysis begins with characterized genes. If no relevant alterations are identified in characterized genes, analysis continues to candidate genes.
Trio samples are required for candidate gene analysis.
ExomeNext has been used to successfully identify both inherited and de novo causative gene
mutations in a diverse variety of single gene and mitochondrial disorders. Our ExomeNext
detection rate is 30% for characterized genetic etiologies, and an additional 8% among
candidate genetic etiologies.1,2
ExomeNext Detection Rates
30%
Positive/Likely positive among
characterized genetic etiologies
Positive/Likely positive among
candidate genetic etiologies
53%
8%
Uncertain among characterized
genetic etiologies
Negative
9%
1. Farwell K, et al., Genet Med., 2014
2. Farwell Hagman K, et al., Genet Med., 2016
ambrygen.com
co n g en ita l a n om a li e s
5
multiple congenital anomalies
Many people with genetic disorders are born with multiple congenital anomalies, or physical
characteristics that make them distinctive. Determining the underlying cause is often based on
recognizing a pattern of characteristics, which can involve several body systems.
Testing Menu Highlights:
Noonan syndrome (NS)
NS is a common inherited condition
associated with a range of clinical
features and severity. Mild cases
may affect as many as 1 in 100 births.
Typical clinical features of NS are
short stature, congenital heart
defects, and developmental delay.
Our panel includes the four most
common genes associated with NS.
Cornelia de Lange
syndrome (CdLS)
Prader-Willi syndrome (PWS)
CdLS affects multiple body
systems, resulting in
characteristic facial features,
limb defects, growth retardation,
and intellectual disability. Our
CdLSNext panel includes all five
genes implicated in CdLS.
PWS is associated with
hypotonia in infancy, characteristic
facial features and behaviors
(including excessive eating and
food-seeking behavior), and
intellectual disability. Our testing
includes methylation studies of
chromosome 15q11-13, the region
implicated in PWS.
Multiple Congenital Anomalies Testing Menu
condition name
gene(s)
tat (weeks)
Alagille syndrome
JAG1
2-4
CHARGE syndrome
CHD7
2-4
RPS6KA3
2-4
HDAC8, NIPBL, RAD21, SMC1A, SMC3
2-4
EHMT1
2-4
OCRL
2-4
KRAS, PTPN11, RAF1, SOS1
2-4
OFD1
2-4
methylation studies of 15q11-13
1-2
CREBBP
2-4
GPC3
2-4
DHCR7
2-4
Smith-Magenis syndrome
RAI1
2-4
Sotos syndrome
NSD1
2-4
Coffin-Lowry syndrome
Cornelia de Lange syndrome
Kleefstra syndrome
Lowe syndrome
Noonan syndrome
Oral-facial-digital syndrome
Prader-Willi syndrome
Rubinstein-Taybi syndrome
Simpson-Golabi-Behmel syndrome
Smith-Lemli-Opitz syndrome
n eu ro d e v elo pm en ta l d i s o r d er s
6
neurodevelopmental disorders
2-3% of individuals in the U.S. are diagnosed with intellectual disability (ID)1 and 1-2% of
children in the U.S. are found to have an autism spectrum disorder (ASD).2 ID and ASDs can
be syndromic (occurring with other medical problems) or non-syndromic (isolated). Genetic
testing can help to confirm the underlying cause for up to 40% of affected individuals.
We offer a range of single syndrome testing and multi-gene panels for individuals with neurodevelopmental disorders
(listed in blue below). These and many of our other tests can be combined to meet the individual needs of patients and
their families.
patient with unexplained id and/or asd
Does this patient have features of a recognizable genetic syndrome?
yes
Specific genetic
testing for the
suspected syndrome
no
Chromosomal Microarray and Fragile X Testing
Does this patient have ID/ASD in conjunction with epilepsy?
no
yes
Neurodevelopment-Expanded
IDNext or
AutismFirst/AutismNext
ExomeNext
1
2
Larson SL, et al. Minneapolis, MN: Institute on Community Integration, University of Minnesota. 2000.
Centers for Disease Control and Prevention. MMWR Surveill Summ, 2012.
ambrygen.com
epilepsy
7
epilepsy
Epilepsy is a common condition that affects about 1 in every 26 people, with approximately
150,000 new cases diagnosed in the U.S. per year.1 An increasing number of medical
management decisions are based on the results of genetic testing.
Causes of Epilepsy2
structural /acquired
•
•
•
•
•
Stroke
Trauma
Congenital lesions
Neoplasms
Other
other
c ause s
genetic
g ene tic
c ause s
•
•
•
•
Single gene
Complex inheritance
Modifiers
Susceptibility alleles
Our flexible range of epilepsy tests and other options can help, depending on the situation:
•
•
•
•
Smaller, targeted panels minimize cost, turnaround time, and the potential for variants of uncertain clinical significance
Larger, broad panels maximize detection rates
Reflex options allow you to start small and test in a step-wise fashion
Chromosomal microarray and ExomeNext (diagnostic exome sequencing) can supplement panel testing
EpiFirst: Phenotype-specific epilepsy panels targeting the most likely causative genes
• EpiFirst-Neonate: 10 genes associated with neonatal seizures
• EpiFirst-Fever: 13 genes associated with febrile seizures
• EpiFirst-IS: 17 genes associated with infantile spasms
• EpiFirst-Focal: 11 genes associated with non-lesional focal epilepsy
EpilepsyNext: Broad epilepsy panel with 100 well-characterized and newer epilepsy genes
CustomNext-Epilepsy: Customize epilepsy genetic testing for your patients. Select any combination of the 100 genes on
EpilepsyNext panel.
Neurodevelopment-Expanded: Comprehensive 196-gene panel for patients with epilepsy in conjunction with ID, ASDs, or both
1. Institute of Medicine of the National Academies. March 20, 2012.
2.Thomas RH and Berkovic SF, Nat Rev Neurol., 2014.
i n h er it ed m e ta b o li c d i s o r d er s
8
inherited metabolic disorders
Inherited metabolic disorders can pose serious complications at various ages. Early diagnosis
and treatment (if available) can significantly impact prognosis and outcome.
Lysosomal storage disorders (LSDs)
LSDs are inherited metabolic disorders that cause an abnormal build-up of various toxic materials in the body’s cells as a
result of enzyme deficiencies. LSDs can affect different parts of the body, including the bones, brain, skin, heart, and
central nervous system. About one in every 5,000 babies is born with an LSD and we offer testing for some of the most
common disorders:
condition name
gene(s)
tat (weeks)
PPT1, TPP1, CLN3, DNAJC5, CLN5, CLN6, MFSD8,
CLN8, CTSD, GRN, ATP13A2, CTSF, KCTD7
4-6
CLN3
2-4
PPT1
2-4
TPP1
2-4
CTSD
2-4
Gaucher disease
GBA
2-4
Hunter syndrome/Mucopolysaccharidosis
(MPS) type 2
IDS
2-4
NPC1, NPC2
2-4
HEXA
2-4
Batten disease/Neuronal ceroid
lipofuscinosis (NCL)
Niemann-Pick disease, type C
Tay-Sachs disease
Leukodystrophies
Leukodystrophies are disorders that affect the central nervous system by disrupting the growth or maintenance of the
myelin sheath, which insulates nerve cells. These disorders affect at least 1 in every 7,600 babies and we offer testing for
several of the most common:
condition name
gene(s)
tat (weeks)
Canavan disease
ASPA
2-4
Pelizaeus-Merzbacher disease
PLP1
2-4
ABCD1
2-4
X-linked adrenoleukodystrophy (X-ALD)
ambrygen.com
pulmonology
9
pulmonology
As the first diagnostic laboratory to offer sequencing for CFTR, the gene associated with
cystic fibrosis, we have a longstanding commitment to the accurate diagnosis of inherited
pulmonary disorders.
CF: CFTR mutation detection
rate by testing option
Testing Menu Highlights:
CF is the most common autosomal recessive condition in
the Caucasian population. It has a wide range of severity,
and primarily affects the respiratory and digestive systems.
We offer several options for analysis of the CFTR gene,
as well as a highly sensitive and carefully designed
mutation panel.
% clinically affected individuals
Cystic fibrosis (CF)
100%
Primary ciliary dyskinesia (PCD)
80%
41%
60%
38%
40%
20%
21%
0%
CFTR mutation detection by test type
PCD is believed to be underdiagnosed. It can cause
pulmonary difficulties as well as multiple congenital
anomalies, such as situs inversus or situs ambiguous.
Our PCDNext panel includes the genes most commonly
associated with PCD.
CF Amplified
CF102
ACMG-defined common mutations
Pulmonology Testing Menu
condition name
gene(s)
tat
Alpha-1 antitrypsin deficiency
SERPINA1
2-4 weeks
Congenital central hypoventilation syndrome
PHOX2B
2-4 weeks
CFTR
5-14 days
ARMC4, CCDC39, CCDC40, CCDC103,
CCDC114, CFTR, DNAAF1, DNAAF2,
DNAAF3, DNAAF5, DNAH5, DNAH11,
DNAI1, DNAI2, LRRC6, OFD1, RPGR,
RSPH4A, RSPH9, SPAG1, NME8 (TXNDC3)
4-5 weeks
ABCA3, SFTPB, SFTPC
5-14 days
TERC, TERT
2-4 weeks
Cystic fibrosis
Primary ciliary dyskinesia (PCDNext)
Surfactant dysfunction
(respiratory distress syndrome)
Telomere-related pulmonary fibrosis
va scul ar disorder s
10
vascular disorders
Disorders of the vascular system can include the arteries, veins, and capillaries that carry blood
to and from the heart. Problems of the vascular system are common and can be serious;
confirming a diagnosis can be helpful to direct medical management in a timely manner.
Testing Menu Highlights:
Hereditary hemorrhagic telangiectasia (HHT)
Thoracic aortic aneurysms/dissections (TAAD)
Hereditary hemorrhagic telangiectasia (HHT) is an
inherited condition causing abnormalities in the blood
vessels. Frequent nosebleeds, characteristic skin findings,
and blood vessel malformations are common. Establishing
a genetic diagnosis not only guides management for
patients, but also identifies family members that may
benefit from life-saving screening and treatment.
Some people have an increased risk for TAAD, which, if
untreated, have a high morbidity and mortality rate.
Identifying individuals at risk for TAAD is complicated
by the fact that sudden death is often the first major
clinical sign. Establishing a molecular diagnosis for
these conditions can direct medical management of
cardiovascular complications. This is critical to
preventing an aortic dissection, which is often fatal.
Vascular Disorders Testing Menu
condition name
test
gene(s)
tat (weeks)
HHTFirst
ACVRL1, ENG, SMAD4
2-3
HHTNext
ACVRL1, ENG, SMAD4, GDF2, RASA1
2-3
Thoracic aortic aneurysms/dissections
TAADNext
22 genes
2-4
Ehlers-Danlos syndrome, vascular type
EDS IV
COL3A1
2-4
Hereditary hemorrhagic telangiectasia
ambrygen.com
cardiology
11
cardiology
Clinical signs can be subtle and sudden
death may be the first sign of inherited
cardiovascular disorders; establishing a
molecular diagnosis can be life-saving.
Genetic test results can direct patient
management, surveillance, lifestyle
recommendations, and risk assessment
for family members.
Heart Rhythm Society (HRS) and European
Heart Rhythm Association (EHRA) Guidelines
Genetic testing is recommended for all patients with:
• Hypertrophic cardiomyopathy (HCM)
Flexible Testing
Our menu features tiered panels to minimize turnaround
time and help control costs. Additionally, we offer
comprehensive panel options to maximize detection
rates and offer customizable testing based on your
patient's clinical presentation.
• Dilated cardiomyopathy (DCM) and cardiac
conduction disease
• Dilated cardiomyopathy (DCM) and a family history
of sudden death
• Suspicion of long QT syndrome (LQTS)
• Suspicion of catecholaminergic polymorphic
ventricular tachycardia (CPVT)
Adapted from Ackerman MJ, et al. Heart Rhythm. 2011 Aug;8(8):1308-39.
Testing Menu Highlights:
FHNext
TAADNext
A next generation sequencing panel of the 3 most
common genes associated with FH. FHNext also includes
gross deletion/duplication analysis of the LDLR gene.
A next generation sequencing panel of 22 genes associated
with thoracic aortic aneurysms and dissections, Marfan
syndrome, or related disorders. Gross deletion/duplication
analysis is performed for 17 genes.
RhythmFirst and RhythmNext
CardioNext
12-gene and 36-gene tiered next generation sequencing
and gross deletion/duplication panels for inherited
arrhythmias like long QT syndrome, Brugada syndrome,
and more.
A next generation sequencing panel of 85 genes (if including
the TTN gene) associated with arrhythmias, cardiomyopathies,
and other inherited cardiovascular conditions. Gross deletion/
duplication analysis is performed for 83 genes.
HCMFirst and HCMNext
2-gene and 27-gene tiered next generation sequencing and gross deletion/duplication panels for hypertrophic cardiomyopathy.
cardiology
12
Familial Hypercholesterolemia (FH)
FH due to a genetic cause occurs in about 1 in 200 individuals worldwide and is more common in certain populations.
FH causes extremely high levels of low density lipoproteins cholesterol (LDL-C), increasing the risk for premature coronary
artery disease (CAD), myocardial infarction, and atherosclerotic plaque formation. Early detection by genetic testing may
lead to earlier treatment, and can greatly reduce the risk of a severe coronary event.
Screening for FH
Studies suggest that only 10% of those with FH are aware of their condition and receiving the care they need. Effective
screening to identify index cases and subsequent cascade screening of family members is critical to ensure early
treatment for those with FH.
Cardiology Testing Menu
condition name
test
tat (weeks)
Arrythmias
RhythmFirst: 12 genes
2-3
RhythmNext: 36 genes
4-5
CPVTNext: 6 genes
4-5
CMNext (+TTN): 55 genes
4-5
DCMNext: 36 genes
4-5
HCMFirst: MYBPC3, MYH7
2-3
HCMNext: 27 genes
4-5
Arrhythmogenic right ventricular dysplasia
(ARVD)
ARVDNext: 9 genes
4-5
Left ventricular non-compaction (LVNC)
LVNCNext: 8 genes
4-5
Arrhythmias, inherited (long QT syndrome,
Brugada syndrome, and others)
Catecholaminergic polymorphic ventricular
tachycardia (CPVT)
Cardiomyopathies
Cardiomyopathy, inherited
Dilated cardiomyopathy (DCM)
Hypertrophic cardiomyopathy (HCM)
Thoracic aortic aneurysms/dissections, Marfan syndrome, related disorders
Marfan syndrome, thoracic aortic aneurysms/
dissections (TAAD), and related disorders
Marfan syndrome (MFS)
Ehlers-Danlos syndrome, vascular type (EDS IV)
TAADNext: 22 genes
2-4
CustomNext-TAAD: up to 22 genes
2-4
FBN1
2-4
COL3A1
2-4
FHNext: APOB, LDLR, PCSK9
2-3
CardioNext (+TTN): 85 genes
4-5
CustomNext-Cardio: up to 85 genes
4-5
Familial hypercholesterolemia
Familial hypercholesterolemia (FH)
Comprehensive Cardiovascular Testing
Arrhythmias and cardiomyopathy, inherited
ambrygen.com
gastroenterology
13
gastroenterology
Genetic conditions with gastrointestinal involvement can pose serious lifetime complications
and possibly increase the risk of cancer. As the first diagnostic laboratory to offer molecular
genetic testing for pancreatitis, we have a longstanding commitment to the accurate diagnosis
of inherited gastrointestinal disorders.
Testing Menu Highlight:
Pancreatitis
Chronic (or recurrent acute) pancreatitis may be caused
by environmental or genetic factors. It is characterized
by recurring inflammatory attacks that gradually cause
irreversible damage to the pancreas and surrounding
tissue. Understanding the underlying genetic cause of
pancreatitis may change lifestyle choices and treatment
of affected individuals. We offer a panel of 4 genes
associated with chronic or recurrent acute pancreatitis in
order to provide an accurate diagnosis for your patients.
American College of Gastroenterology Guideline
Genetic testing for pancreatitis should be considered in
patients with pancreatitis <30 years old.
Adapted from Tenner S, et al. Am J Gastroenterol. 2013.
Gastroenterology Testing Menu
condition name
Alagille syndrome
gene(s)
tat
JAG1
2-4 weeks
SERPINA1
2-4 weeks
Cystic fibrosis
CFTR
5-14 days
Familial adenomatous polyposis (FAP)
APC
14-21 days
SERPING1
2-4 weeks
Hirschsprung disease, RET-related
RET
1-4 weeks
Juvenile polyposis syndrome (JPS)
BMPR1A, SMAD4
14-21 days
PRSS1, SPINK1, CFTR, CTRC
2-4 weeks
Peutz-Jeghers syndrome (PJS)
STK11
10-21 days
Wilson disease
ATP7B
2-4 weeks
APC, ATM, BRCA1, BRCA2,
CDKN2A, EPCAM, MLH1, MSH2,
MSH6, PALB2, PMS2, STK11, TP53
14-21 days
Alpha-1 antitrypsin deficiency
Hereditary angioedema
Pancreatitis
Hereditary pancreatic cancer (PancNext)
endocrinology
14
endocrinology
Genetic conditions with endocrine system involvement can pose serious health complications
and/or increased risks for tumors at various ages. Early diagnosis and treatment (if available)
can significantly impact prognosis and outcome.
Testing Menu Highlights:
Maturity-onset diabetes of the young (MODY)
Multiple endocrine neoplasia type 1 (MEN1)
MODY is commonly diagnosed in late childhood to early
adulthood, with development of non-insulin dependent
diabetes prior to 25 years of age as a defining feature.
Given this, many individuals with MODY are misdiagnosed
with type 1 or type 2 diabetes. Our panel includes the
five genes most commonly implicated in MODY and
80-85% of patients with MODY will have a mutation in
one of these genes.
MEN1 is characterized by endocrine and non-endocrine
tumors mainly involving the parathyroid, anterior
pituitary and the pancreas. Generally, primary
hyperparathyroidism is the first clinical manifestation
The majority (94%) of patients carrying a MEN1 gene
mutation exhibits at least one symptom by age 50.
Mutations in MEN1 are detected in approximately
80-90% of affected individuals.
Hereditary paraganglioma/pheochromocytoma (PGL/PCC)
PGLs are neuroendocrine tumors of the autonomic nervous system originating from the external ganglia. Pheochromocytomas
PCCs are PGLs that are confined to the adrenal medulla. ~75% of PGL/PCCs are benign; however, morbidity and mortality are
associated with high levels of circulating catecholamines, which can lead to. Up to 30% of individuals with PGL/PCCs have a
germline mutation in one of the known susceptibility genes.
Endocrinology Testing Menu
condition name
Maturity-onset diabetes of the young (MODY)
gene(s)
tat
HNF1A, GCK, HNF1B, HNF4A, PDX1
4-5 weeks
MEN1
14-21 days
RET
14-21 days
MAX, SDHA, SDHAF2, SDHB,
SDHC, SDHD, TMEM127
14-21 days
FH, MAX, MEN1, NF1, RET, SDHA,
SDHAF2, SDHB, SDHC, SDHD,
TMEM127, VHL
14-21 days
von-Hippel Lindau (VHL) disease
VHL
14-21 days
Neurofibromatosis type 1 (NF1)
NF1
14-21 days
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)
FH
14-21 days
PRKAR1A
14-21 days
Multiple endocrine neoplasia type 1 (MEN1)
Multiple endocrine neoplasia type 2 (MEN2A, MEN2B, and
familial medullary thyroid carcinoma (FMTC))
Hereditary paraganglioma/pheochromocytoma non-syndromic (PGLFirst)
Hereditary paraganglioma/pheochromocytoma - comprehensive
(PGLNext)
Carney complex
ambrygen.com
n eu ro cu ta n eo u s / n eu ro - o n co lo g y
15
neurocutaneous/neuro-oncology disorders
Neurocutaneous and neuro-oncological disorders can cause tumors in the brain and spinal cord.
Neurocutaneous disorders can also affect other organ systems, such as the eyes, kidneys, and
heart. These disorders cause tumors that can be benign or malignant and often require medical
or surgical intervention. Accurate diagnosis often involves a combination of clinical assessment
and diagnostic testing.
Testing Menu Highlights:
Neurofibromatosis 1 (NF1)
NF1 can cause skin, eye, bone, and
vascular problems, as well as
learning disabilities and multiples
tumors. Mutations in the NF1 gene
can be identified for the majority
of people with NF1.
Tuberous sclerosis complex
(TSC)
TSC can cause multiple skin and kidney
problems, as well as intellectual
disability, epilepsy, and brain tumors.
Mutations in the TSC1/TSC2 genes can
be identified for most people with TSC.
Li-Fraumeni syndrome (LFS)
LFS causes a broad spectrum of
brain tumors including
astrocytomas, glioblastomas,
medulloblastomas, and choroid
plexus carcinomas. LFS also causes
many non-nervous system tumors.
Neurocutaneous/Neuro-Oncology Disorders Testing Menu
condition name
gene(s)
tat
ATM
2-3 weeks
PRKAR1A
14-21 days
ACVRL1, ENG, SMAD4, GDF2, RASA1
2-4 weeks
SPRED1
2-3 weeks
Li-Fraumeni syndrome (LFS)
TP53
10-21 days
Neurofibromatosis 1 (NF1)
NF1
2-3 weeks
PTCH1
14-21 days
Tuberous sclerosis complex (TSC)
TSC1, TSC2
2-3 weeks
von Hippel-Lindau (VHL) disease
VHL
14-21 days
AIP, ALK, APC, CDKN1B, CDKN2A,
DICER1, MEN1, MLH1, MSH2, MSH6,
NBN, NF1, NF2, PHOX2B, PMS2,
POT1, PRKAR1A, PTCH1, PTEN,
SMARCA4, SMARCB1, SMARCE1,
SUFU, TP53, TSC1, TSC2, VHL
14-21 days
Ataxia-telangiectasia (A-T)
Carney complex
Hereditary hemorrhagic telangiectasia (HHT)
Legius syndrome
Nevoid basal cell carcinoma (Gorlin syndrome)
Hereditary brain tumors (BrainTumorNext)
p e d i at r i c o n co lo g y
16
pediatric oncology
Hereditary cancer syndromes in children and adolescents may be underdiagnosed, but are
becoming more recognized. Genetic testing can help clarify a diagnosis, opening the door to
timely treatment and intervention.
Testing Menu Highlight:
Hereditary retinoblastoma
Retinoblastoma (RB) is an intraocular malignancy of the developing retina associated with germline and/or somatic mutations
of the RB1 tumor suppressor gene. RB is a; typically presents in the first 5 years of life. The most common sign of RB is
leukocoria or "cat's eye reflex." Other symptoms of retinoblastoma include strabismus, irritation, redness, persistent eye pain
and vision impairment in the affected eye. Approximately 60% of RB is unilateral; the other 40% of cases are bilateral.
Pediatric Oncology Testing Menu
condition name
Constitutional mismatch repair deficiency (CMMRD)
Hereditary paraganglioma/pheochromocytoma comprehensive analysis (PGLNext)
Hereditary retinoblastoma
Li-Fraumeni syndrome (LFS)
Pleuropulmonary blastoma familial tumor
predisposition snydrome
Hereditary brain tumors (BrainTumorNext)
gene(s)
tat (days)
MLH1, MSH2, MSH6, PMS2, EPCAM
14-21
FH, MAX, MEN1, NF1, RET, SDHA, SDHAF2,
SDHB, SDHC, SDHD, TMEM127, VHL
14-21
RB1
14-21
TP53
10-21
DICER1
14-21
AIP, ALK, APC, CDKN1B, CDKN2A, DICER1,
MEN1, MLH1, MSH2, MSH6, NBN, NF1, NF2,
PHOX2B, PMS2, POT1, PRKAR1A, PTCH1,
PTEN, SMARCA4, SMARCB1, SMARCE1,
SUFU, TP53, TSC1, TSC2, VHL
14-21
ambrygen.com
h em ato lo g y- o n co lo g y
17
hematology-oncology
Genetic conditions with hematologic involvement can cause health complications at any age.
Some symptoms, like bone marrow failure, may be associated with an increased risk for cancer.
Testing Menu Highlight:
Diamond-Blackfan anemia (DBA)
DBA is an inherited bone marrow failure syndrome, which typically presents in the first year of life. It may be associated with
physical malformations, an increased risk for leukemia, and blood abnormalities. Clinical variability can be wide, so some
individuals may not be properly diagnosed by clinical assessment alone. Mutations can be found in up to 65% of individuals with
a clinical diagnosis of DBA by gene sequencing and gross deletion/duplication analysis of the 11 genes listed below.
Hematology-Oncology Testing Menu
condition name
gene(s)
Diamond-Blackfan anemia (DBA)
Dyskeratosis congenita
tat (weeks)
RPS19, RPL5, RPS10, RPL11,
RPL35A, RPS26, RPS24, RPS17,
RPS7, RPL19, RPL26
2-4
DKC1, NHP2, NOP10, TERC,
TERT, TINF2, WRAP53
2-4
SBDS
2-4
Shwachman-Diamond syndrome
Amount of DBA attributed to pathogenic variants by gene1
~25%
~6.6%
~6.4%
~4.8%
~3%
~2.6%
RPS19
1
RPL5
RPS10
RPL11
RPL35A
~2%
RPS26
Clinton C and Gazda HT., GeneReviews®., 2009 (updated 2016).
RPS24
~1%
~1%
Rare
Unknown
RPS17
RPS7
RPL26
RPL19
oncology
18
oncology
On average, 5-10% of all cancers are hereditary. This percentage can vary depending on the
cancer type. It is important to gather details about personal and family history when evaluating
for hereditary cancer.
Red Flags for Hereditary Cancer
3 or more
multiple
cancers on the same
side of the family
Testing Menu Highlight
2 or more
CancerNext
primary cancers
in the same person
any of the following cancers diagnosed <50 years
young
Breast, colorectal, uterine
A next generation sequencing
panel of 32 genes associated
with increased risk for at least
one of 8 major cancers, including
breast, colorectal, ovarian, and
uterine cancer.
personal or family history of any of the following:
rare
Male breast cancer, ovarian cancer, endocrine tumors
Oncology Testing Menu*
cancer/tumor type
Breast/gynecologic
Colorectal
Genitourinary
Melanoma
Nervous system
Pancreatic
Paraganglioma/pheochromocytoma
Comprehensive (multi-cancer)
test
tat (days)
BRCAplus (6 genes)
7-14
BRCAplus-Expanded (8 genes)
14-21
BreastNext (17 genes)
14-21
GYNplus (13 genes)
14-21
OvaNext (24 genes)
14-21
ColoNext (17 genes)
14-21
RenalNext (19 genes)
14-21
ProstateNext (14 genes)
14-21
MelanomaNext (8 genes)
14-21
BrainTumorNext (27 genes)
14-21
PancNext (13 genes)
14-21
PGLFirst (7 genes)
14-21
PGLNext (12 genes)
14-21
CancerNext (32 genes)
14-21
CancerNext-Expanded (67 genes)
14-21
CustomNext-Cancer (up to 67 genes)
14-21
*Other hereditary cancer test options are available, visit ambrygen.com/hereditary-cancer-panels for more information on panels and single gene testing.
ambrygen.com
test ordering
19
test ordering
Our ordering process is as simple as possible because we know
you are busy. Help is available at any step in the process.
1 | order test kits
You can order our test kits three ways:
• Online at ambrygen.com/order-sample-kit
• By email at [email protected]
• By phone at 949-900-5798
2 | complete test requisition forms
Our Comprehensive Test Requisition Form (TRF) is
included in test kits. This and specialty-specific TRFs are
online at ambrygen.com/forms. For a quick and seamless
way to order testing from your computer or mobile
device, our secure online client portal (AmbryPort2.0) is
available (more details below).
3 | we confirm insurance benefits for you
For insurance billing, Ambry is contracted with the majority
of U.S. health plans and offers preverification of insurance
coverage for genetic testing. You can complete our online
automated preverification request form at ambrygen.com/
insurance-preverification-request-form or complete a
Preverification of Benefits Form and fax it to our
Insurance Verification department at +1-949-900-5501
with a copy of your patient’s insurance card. Please call
us at +1-949-900-5794 or email preverification@
ambrygen.com with any preverification questions.
4 | ship sample to ambry genetics
5 | securely track sample and results
Package sample(s) in the pre-paid shipping envelope
according to our test kit instructions. All specimen
requirements are found at ambrygen.com/
specimen-requirements.
AmbryPort2.0 is a secure, HIPAA-compliant online client
portal that allows many services. Read more about
AmbryPort2.0 and its features later in this booklet.
Sign up for an AmbryPort2.0 account online at portal.
ambrygen.com/signup/ or contact Client Services at
949-900-5500. A user guide and additional information
can be found at ambrygen.com/ap2.
test ordering
20
AmbryPort2.0
AmbryPort2.0 is an online customer interface, which includes features such as:
•
•
•
•
•
•
Insurance preverification and order submission
Ability to get status updates and track samples
Ability to print and/or download patient reports
Patient-specific auto-generation of letters of medical necessity
Patient signature form to easily obtain patient signature during clinic
Ability to upload insurance paperwork, medical records and other patient-specific documents
System Requirements
• Compatible with: desktop, tablet and mobile devices
• AmbryPort 2.0 works with: Safari, Chrome, Firefox, and Internet Explorer Version 8 or higher
• We recommend using the most current browser version to insure full functionality of the AmbryPort 2.0 interface
Specimen Requirements
Blood: Collect 3-5cc (adult) or 2cc (child) minimum whole blood in purple top (EDTA) tube (preferred) or yellow top
(citric acetate) tube. Grey top (potassium oxalate/sodium fluoride) tube also accepted. Store at room temperature or
refrigerate. Ship at room temperature for two-day delivery.
Saliva: Fill 1 tube (2 tubes for pediatric patients) with saliva up to black line (1cc of saliva) in Oragene Self Collection
container. Close tube; 1cc of buffer will mix with saliva for a total volume of 2cc. Store at room temperature in sterile bag.
Ship at room temperature for two-day delivery.
DNA: 5μg of DNA in TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 100μl at ~50ng/μl. Please provide DNA OD
260-280 ratio (preferred 1.7-1.9) and send agarose picture with high mw genomic DNA, if available. Store at -20°C. Ship
frozen on dry ice (preferred) or ice for next-day delivery.
Post-mortem samples: visit ambrygen.com/post-mortem-cardiovascular-genetic-testing or contact your local Ambry
representatives to discuss these (e.g. frozen or FFPE tissue, blood spots) and special pricing.
Blood spots: Blood spots are accepted for many tests. Minimum of one complete spot ~0.5 inches in diameter on S&S 903
collection paper or similar. Store in sterile bag at room temperature. Ship at room temperature for 2-day delivery.
Prenatal: Prenatal testing is available. Please call an Ambry genetic counselor to discuss your case.
NOTE: Complete specimen requirements can be found at ambrygen.com/specimen-requirements
ambrygen.com
variant a ssessment
21
variant assessment and classification
Accurate classification of a variant of unknown significance (VUS)
is integral to understanding the ramifications of genetic test
results for your patients and their families.
Our testing does not stop at reporting a VUS. Following relevant laboratory guidelines is the baseline, and we take this
several steps further by incorporating layers of evidence that we gain from custom analyses, including those that are
specific to an individual or family.
personalized
computational analysis
Bioinformatics and variant team assessment (including 3D modeling by
structural biologists), literature review, and more
ambry's translational
genomics laboratory
VUS-specific translational and functional studies to better understand the
scope of the variant
family studies program
Segregation analysis for informative family members
(as applicable; see details below)
follow-up as needed
Active reassessment and contact to keep you informed of any VUS
status changes
More details about our variant assessment and classification process can be found at ambrygen.com/variant-classification
Family Studies Program Process
When a VUS is identified and a family is interested in helping to better understand its meaning, an application to our
Family Studies Program is something to consider.
Download and complete the appropriate Family Studies Program paperwork (see ambrygen.com/family-studies-program),
and fax to Ambry Genetics at 949-271-5621 ATTN: Family Studies
•Our Family Studies team will notify you once the application is received and reviewed
• Results are summarized in a Family Studies report for the proband, complete with interpretation by our clinical staff
•Turnaround time: up to 6 months
• Please direct questions to [email protected]
progeny
22
progeny
Progeny’s Family History Questionnaire (FHQ) and Pedigree Software
Gathering and assessing family history data is critical in identifying risk for inherited disorders and determining
personalized management options. Progeny Clinical gives you the tools you need to gather, analyze, and act on family
history – all in one place.
• Collect family history directly from your patients
• Review and edit patient-entered data, and draw complex pedigrees easily
• Run validated hereditary cancer risk assessment models
• Analyze data using custom spreadsheet reports and queries
• Seamlessly order genetic testing from Ambry Genetics and review results from within the software
• Generate auto-populated custom letters, notes, and reports
• Integrate with your institution’s electronic medical record (EMR)
• Get started quickly with ready-to-use templates and cloud database hosting
Sample Progeny Pedigree Utilizing Validated Risk Assessment Models
To learn more about Progeny, visit progenygenetics.com
ambrygen.com
community outreach
23
community outreach
We are committed
to supporting the
communities we serve.
Patient Websites
From our educational patient websites to our many
advocacy activities, we remain dedicated to improving the
lives of patients and their families beyond the genetic
testing process. Please explore our websites for patients
and families at patients.ambrygen.com.
Mauli Ola Foundation
Ambry leadership created the Mauli Ola Foundation in
2006 to promote awareness of genetic diseases. Mauli
Ola supports programs for those with life-threatening
illnesses and provides direct, immediate ways for children
with genetic disorders to enjoy healthy lives through
natural treatments. Mauli Ola Surf Experience and Ocean
Experience Days get kids with genetic conditions into the
ocean to experience what natural therapies can do for their
health and self-esteem. Please visit mauliola.org for more
information.
The world would be a better place if all human disease was understood.
Introducing AmbryShare
AmbryShare is our pledge to share anonymized genomic
data to help understand all human disease. AmbryShare is
comprised of three key pieces: The AmbryShare database,
the scientific community, and patients. Like an ecosystem,
we need all these pieces to work together towards
understanding to the relationships between genetics and
human disease.
AmbryShare Database
One of the largest allele frequency databases with
anonymized aggregate human genome (exome) data on
10,000+ patients with disease.
Scientific Community
Free access to all aggregated variant data from the
sequenced cohort, by disease type, to continue to work
on new breakthroughs, treatments and cures for disease.
Patients
Patients can register with AmbryShare to receive updates,
use our online family history tool to create a pedigree, and
take it to their healthcare provider to discuss if genetic
counseling and/or testing is right for them.
You can learn more and register to access the
AmbryShare database at ambryshare.com.
about ambry
24
about ambry
About Our Services
Support
Board-certified genetic counselors, laboratory directors, and medical directors are readily available to assist with test
selection, case reviews, and result interpretation.
Excellent Coverage, Personalized Support
Ambry offers insurance, institutional and self-pay billing options. For insurance billing, Ambry is contracted with the
majority of U.S. health plans and offers preverification of insurance coverage for genetic testing. Financial options and
dedicated billing specialists are available to help your patients access the genetic testing they need. Have your patients
call or email our Billing department at +1-949-900-5795 or [email protected] with any questions.
About Ambry Genetics
Ambry Genetics is a privately-held healthcare company with the most comprehensive suite of genetic testing solutions
for inherited and non-inherited diseases. Since 1999, Ambry has tested approximately half a million patient samples
benefiting 90% of all U.S. patients covered by public and private insurers. Ambry is dedicated to scientific collaboration
by offering its rapidly growing database of anonymized genomic data (variant frequencies) free to the global medical
research community to fulfill the promise of the human genome to cure or manage all human disease. Ambry is
dedicated to the belief that human health should not be patented or owned, and genomic data should be freely shared
so we can try to understand all human disease.
To order your prepaid sample submission kits, please contact:
Ambry Genetics
15 Argonaut
Aliso Viejo, CA 92656 USA
+1 866-262-7943
[email protected]
For more details about these tests, visit ambrygen.com
Complete reference citations used to develop clinical content are available at ambrygen.com
ambrygen.com
COMPPORT | 12.22.16 | 50339.4443_v2
15 Argonaut, Aliso Viejo, CA 92656 USA
Toll Free +1 866 262 7943
Fax +1 949 900 5501