Download 12.04.518 Preconception Testing for Carrier Status of Genetic

MEDICAL POLICY – 12.04.518
Preconception Testing for Carrier Status of Genetic
Diseases
BCBSA Ref. Policies: 2.04.104, 2.04.83
Effective Date: Aug. 1, 2016
RELATED MEDICAL POLICIES:
Last Revised:
July 12, 2016
12.04.93
Replaces:
12.04.107
12.04.519 Genetic Testing for Alpha –Thalassemia
Genetic Cancer Susceptibility Panels Using Next Generation Sequencing
Select a hyperlink below to be directed to that section.
POLICY CRITERIA | CODING | RELATED INFORMATION
EVIDENCE REVIEW | REFERENCES | HISTORY
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Introduction
Genetic tests are laboratory tests that measure changes in human DNA, chromosomes, genes or
gene products (proteins). Blood, skin, cheek swabs, and amniotic fluid are some common
samples that can be tested. Genetic testing for carrier status is done on people planning a
pregnancy. The goal is to see if they have a potential disease that could be passed onto their
offspring. For certain disorders a carrier state exists where a person has no symptoms of the
disease, but has the potential to pass the disease onto their children, because they carry a gene
for the disease. Often it takes at least two copies of the gene for the disease to cause symptoms.
Usually carrier testing is done before conception when individuals are planning a pregnancy, but
may also be done in the early stages of pregnancy.
Note:
The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The
rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for
providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can
be a place where medical care is given, like a hospital, clinic, or lab. This policy informs providers about when
a service may be covered.
Policy Coverage Criteria
Expanded Carrier
Test Type
Medical Necessity
Expanded Carrier
Expanded carrier screening panels which test for mutations on
Screening Panels
many different genes are considered not medically necessary.
Based on the individual tested, a subset of the panel may be
covered when the policy criteria are met.
Expanded carrier panel test names, and their individual mutation
components, are rapidly evolving. Examples of tests addressed in
this policy include but are not limited to:

Counsyl™ (Counsyl)

GoodStart Select™ (GoodStart Genetics)

Inherigen™ (GenPath)

InheriGen Plus

Inheritest™ (LabCorp)

Natera One™ Disease Panel (Natera)
Notes: For GoodStart Select the provider may select/limit mutations to those
which are targeted to a specific population and in some instances this
would not be considered an expanded panel.
American College of Medical Genetics (ACMG) defines expanded panels
as those that use next generation sequencing to screen for mutations in
many genes, as opposed to gene-by-gene screening (e.g., ethnic-specific
screening or pan-ethnic testing for cystic fibrosis). An ACMG position
statement states that although commercial laboratories offer expanded
carrier screening panels, there has been no professional guidance as to
which disease genes and mutations to include.1Expanded panels may
include the diseases that are present with increased frequency in specific
populations, but typically include testing for a wide range of diseases for
which the patient is not at risk of being a carrier.
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The General Population
Genetic Disease
Coverage Criteria
Cystic Fibrosis
Covered for all individuals with a panel that tests the most
common genes (CPT 81220)
Note:
Carrier testing for cystic fibrosis using CPT 81223 “CFTR (e.g. cystic
fibrosis) gene analysis; full gene sequence” is considered not medically
necessary for carrier testing.
Spinal Muscular Atrophy
Covered for all individuals
Specific Groups or Populations
The following genetic testing may also be considered medically necessary due to an increased
frequency of certain disorders in groups or populations:
Genetic Disease
Medical Necessity
Ashkenazi Jewish Founder
When the individual meets one of the following criteria:
Mutations:


Bloom syndrome

Canavan disease

Cystic fibrosis

Familial dysautonomia

Fanconi anemia (group C)

Gaucher disease

Mucolipidosis IV

Niemann-Pick (type A)

Tay-Sachs disease
Ashkenazi Jewish ancestry consisting of a minimum of one
Jewish grandparent.

If the Jewish partner has a positive carrier test result, the other
partner (regardless of ethnic background) should be screened
only for that identified mutation.
Genetic testing for Askenazi Jewish Founder mutation is
considered not medically necessary for all other uses.
FMR1 Mutations (Including
When any of the following criteria are met:
Fragile-X Syndrome)

Individuals of either sex with intellectual disability,
developmental delay, or autism spectrum disorder

Individuals with a family history of fragile X syndrome or a
family history of undiagnosed intellectual disability

Mothers who are known carriers to determine whether the
fetus inherited the normal or mutant FMR1 gene
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Genetic Disease
Medical Necessity

Affected individuals or relatives of affected individuals who
have had a positive cytogenetic fragile X test (less accurate
historic test) result who are seeking further counseling related
to the risk of carrier status
FMR1 Mutations (Including Fragile-X Syndrome) is considered
not medically necessary for all other uses.
Alpha-Thalassemia –
When ALL of the following criteria are met:
Preconception (Carrier)

Testing
At least one parent is of a high-risk ethnic group, such as
Southeast Asian, African or Mediterranean ancestry

At least one parent has had abnormal biochemical testing
which may include ANY of the following:
o
Anemia
o
Microcytosis ( a low MCV – small blood cells)
o
Hypochromia (a low MCH or MCHC – red blood cells with
less hemoglobin)
o
Abnormal hemoglobin electrophoresis
Genetic testing for hemoglobinopathies, except for alpha
thalassemia, is considered not medically necessary.
Other Inherited Disorders
Carrier testing may be considered medically necessary based on the following general criteria:
Genetic Disease
Medical Necessity
Carrier Testing Specific
When any of the following are present:
Disorder

One or both parents have a first- or second-degree relative
who has the disorder:
o
1st-degree relatives are parents, siblings, and children.
o
2nd-degree relatives are grandparents, aunts, uncles,
nieces, nephews, grandchildren, and half-siblings.

One parent is or both parents are a known carrier of the
disorder.
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Genetic Disease
Medical Necessity
All of the following criteria must also be are met:

The natural history of the disease is understood and the
disease is likely to result in severe health problems in the
homozygous or compound heterozygous state.

Other biochemical or clinical tests to diagnose carrier status are
not available, or provide an indeterminate result or are less
accurate than genetic testing.

The genetic test has adequate sensitivity and specificity to
guide clinical decision making and residual risk is understood
o
The American College of Medical Genetics and Genomics
(ACMG) recommends testing for specific mutations, which
will result in carrier detection rate of 95% or higher for most
disorders.

A clear association of the genetic change with the disorder has
been established
Genetic testing for other specific disorders is considered not
medically necessary when the criteria above are not met.
Coding
If CPT Tier 1 or Tier 2 molecular pathology codes are available for the specific test, they should
be used. If the test has not been codified by CPT, the unlisted molecular pathology code 81479
would be used.
CPT
81223
CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene
analysis; full gene sequence
81412
Ashkenazi Jewish associated disorders genomic sequence panel- Must include at least
9 genes including ASPA, BLM, CFTR, FANCC, GBA, HEXA, IKBKAP, MCOLN1, and
SMPD1
81257
HBA1/HBA2 ( alpha globulin 1 and alpha globulin 2) gene analysis
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CPT
81479
Unlisted molecular pathology procedure
Related Information
Definition of Terms
1st-, 2nd-, or 3rd-degree relative: For the purpose of familial assessment, 1st-, 2nd-, or 3rddegree relatives are blood relatives on the same side of the family (maternal or paternal).The
maternal and paternal sides of the family should be considered independently for familial
patterns of cancer.

1st-degree relatives are parents, siblings, and children.

2nd-degree relatives are grandparents, aunts, uncles, nieces, nephews, grandchildren, and
half-siblings.

3rd-degree relatives are great-grandparents, great-aunts, great-uncles, great-grandchildren,
and first cousins
Carrier testing: Carrier genetic testing is performed on people who display no symptoms for a
genetic disorder but may be at risk for passing it on to their children.
A carrier of a genetic disorder has one abnormal allele for a disorder. Carriers of an autosomal
recessive mutation are typically unaffected. Offspring who inherit the mutation from both
parents usually manifest the disorder. When associated with an autosomal dominant or an Xlinked dominant disorder, the individual may be affected with the disorder or at high risk of
developing the disorder later in life. Women with an X-linked recessive mutation are usually
unaffected. Males receiving a chromosome with an X-linked recessive mutation usually manifest
the disorder.
Compound heterozygous: The presence of two different mutant alleles at a particular gene
locus, one on each chromosome of a pair.
Expressivity/expression: The degree to which a penetrant gene is expressed within an
individual. Genetic testing involves the analysis of chromosomes, DNA, RNA, genes, or gene
products to detect inherited (germline) or non-inherited (somatic) genetic variants related to
disease or health.
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Homozygous: Having the same alleles at a particular gene locus on homologous chromosomes
(chromosome pairs).
Penetrance: The proportion of individuals with a mutation that causes a particular disorder who
exhibit clinical symptoms of that disorder.
Residual risk: The risk that an individual is a carrier of a particular disease, but genetic testing
for carrier status of the disease is negative (e.g., if the individual has a disease-causing mutation
that wasn’t included in the test assay).
Testing sequence: Testing sequence of carrier testing for genetic diseases is generally, the
mother or affected partner is first, and if positive, the other parent is tested.
Evidence Review
Carrier testing is performed to identify couples at risk of having offspring with a genetic disease.
Carriers are usually not at risk of developing the disease, but have a risk of passing a pathogenic
gene mutation to their offspring. Carrier testing may be performed before conception or during
a pregnancy. This policy offers a framework for evaluating the utility of carrier genetic testing.
This policy applies only if there is not a separate policy that outlines specific criteria for carrier
testing. If a separate policy exists, then criteria for medical necessity in that policy supersede the
guidelines in this policy (see Related Policies).
Specific Patient Populations
Carrier screening may be performed for conditions that are found in the general population
(pan-ethnic), for diseases that are more common in particular populations, or based on family
history.
Pan-ethnic (population) screening for carrier status is done for single-gene disorders that are
common in the population, such as cystic fibrosis.
Carrier screening for specific genetic conditions may be done in members of an ethnic group
with a high risk of a specific genetic disorder. For example, certain autosomal recessive
conditions are more prevalent in individuals of Eastern European Jewish (Ashkenazi) descent.
Most individuals of Jewish ancestry in North America are descended from Ashkenazi Jewish
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communities and are therefore at increased risk of being carriers of one of these conditions.
Many of these disorders are lethal in childhood or associated with significant morbidity.
FMR1 Mutations/Fragile-X Syndrome
Fragile-X syndrome is associated with the expansion of the CGG trinucleotide repeat in the
fragile-X mental retardation 1 (FMR1) gene on the X chromosome.
Fragile-X syndrome (FXS) is the most common cause of heritable intellectual disability,
characterized by moderate intellectual disability in males and mild intellectual disability in
females. FXS affects approximately 1 in 4000 males and 1 in 8000 females. In addition to
intellectual impairment, patients present with typical facial features, such as an elongated face
with prominent forehead, protruding jaw, and large ears. Connective tissue anomalies include
hyperextensible finger and thumb joints, hand calluses, velvet-like skin, flat feet, and mitral valve
prolapse. The characteristic appearance of adult males includes macroorchidism. Patients may
show behavioral problems including autism spectrum disorders, sleeping problems, social
anxiety, poor eye contact, mood disorders, and hand-flapping or biting. Another prominent
feature of the disorder is neuronal hyperexcitability, manifested by hyperactivity, increased
sensitivity to sensory stimuli, and a high incidence of epileptic seizures.
Men who are premutation carriers are referred to as transmitting males. All of their daughters
will inherit a premutation, but their sons will not inherit the premutation. Males with a full
mutation usually have intellectual disability and decreased fertility.
Alpha-Thalassemia
Hemoglobin, is the major oxygen carrying protein molecule of red blood cells, consists of 2
alpha (α)-globin chains and 2 beta (β)-globin chains. Alpha-thalassemia refers to a group of
syndromes that arise from deficient production of α-globin chains. Deficient α-globin
production leads to an excess of β-globin chains, which results in anemia by a number of
mechanisms:

Ineffective erythropoiesis in the bone marrow.

Production of nonfunctional hemoglobin molecules.
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
Shortened survival of RBCs [red blood cells] due to intravascular hemolysis and increased
uptake of the abnormal RBCs by the liver and spleen.
The physiologic basis of α-thalassemia is a genetic defect in the genes coding for α-globin
production. Each individual carries four genes that code for α-globin (2 copies each of HBA1 and
HBA2, located on chromosome 16), with the wild genotype (normal) being aa/aa. Genetic
mutations may occur in any or all of these 4 α-globin genes. The number of genetic mutations
determines the phenotype and severity of the α-thalassemia syndromes. The different
syndromes are classified as follows:

Silent carrier (α-thalassemia minima): This arises from one of four abnormal alpha genes
(aa/a-), and is a silent carrier state. A small amount of abnormal hemoglobin can be detected
in the peripheral blood, and there may be mild hypochromia and microcytosis present, but
there is no anemia or other clinical manifestations.

Thalassemia trait (α-thalassemia minor): This is also called α-thalassemia trait and arises
from the loss of 2 α-globin genes, resulting on one of two genotypes (aa/--, or a-/a-). There
is a mild anemia present, and red blood cells are hypochromic and microcytic. Clinical
symptoms are usually absent and in most cases, the Hg electrophoresis is normal.

Hemoglobin H disease (α-thalassemia intermedia): This syndrome results from three
abnormal α-globin genes (a-/--), resulting in a moderate to severe anemia. In HgH disease,
there is an imbalance in α- and β-globin gene chain synthesis, resulting in the precipitation
of excess β chains into the characteristic hemoglobin H, or β-tetramer. This condition has
marked phenotypic variability, but most individuals have mild disease and live a normal life
without medical intervention.
A minority of individuals may develop clinical symptoms of chronic hemolytic anemia. These
include neonatal jaundice, hepatosplenomegaly, hyperbilirubinemia, leg ulcers, and premature
development of biliary tract disease. Splenomegaly can lead to the need for splenectomy, and
transfusion support may be required by the third to fourth decade of life. It has been estimated
that approximately 25% of patients with HgH disease will require transfusion support during
their lifetime. In addition, increased iron deposition can lead to premature damage to the liver
and heart. Inappropriate iron therapy and oxidant drugs should be avoided in patients with HgH
disease.
There is an association between genotype and phenotype among patients with HgH disease.
Individuals with a nondeletion mutation typically have an earlier presentation, more severe
anemia, jaundice, and bone changes, and more frequently require transfusions.
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
Hemoglobin Bart syndrome (α-thalassemia major): This syndrome results from mutations
in all 4 α-globin genes (--/--), resulting in absent production of α-globin chains. This
condition causes hydrops fetalis, which often leads to intrauterine death, or death shortly
after birth. There are also increased complications of pregnancy for a woman carrying a fetus
with hydrops fetalis. These include hypertension, preeclampsia, antepartum hemorrhage,
renal failure, premature labor, and abruption placenta. (See table for probability of
Hoemoglobin Bart Syndrome.)
Alpha-thalassemia is a common genetic disorder, affecting approximately 5% of the world’s
population. The frequency of mutations is highly dependent on ethnicity, with the highest rates
seen in Asians, and much lower rates in Northern Europeans. The carrier rate is estimated to be
1 in 20 in Southeast Asians, 1 in 30 for Africans, and between 1 in 30 and 1 in 50 for individuals
of Mediterranean ancestry. In contrast, for individuals of northern European ancestry, the carrier
rate is less than 1 in 1,000.
Expanded Carrier Screening
New technologies have made it possible to screen for mutations in many genes more efficiently
than testing mutations in a single gene or a small number of population-specific mutations in
several genes. Commercial laboratories offer expanded carrier screening (ECS) panels, which
comprise a nontargeted approach to carrier screening. There is no standardization to the
makeup of these genetic panels; panel composition varies among labs; and different commercial
products for a single condition may test different sets of genes. Although ECS panels may
include conditions that are routinely assessed in carrier testing, ECS panels include many
conditions that are not routinely evaluated and for which there are no existing professional
guidelines.
FMR1 Mutation/Fragile-X Syndrome
Evidence on the clinical benefit of testing for Fragile-X syndrome is largely anecdotal. Clinical
utility of genetic testing can be considered in the following clinical situations: (1) individuals with
a clinical diagnosis of intellectual disability, developmental delay, or autism, especially if they
have any physical or behavioral characteristics of Fragile-X syndrome, a family history of Fragile
X syndrome, or male or female relatives with undiagnosed intellectual disability, and (2)
individuals seeking reproductive counseling.
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Clinical utility for these patients depends on the ability of genetic testing to make a definitive
diagnosis and for that diagnosis to lead to management changes that improve outcomes. No
studies were identified that described how a molecular diagnosis of Fragile-X syndrome
changed patient management. Therefore there is no direct evidence for clinical utility of genetic
testing in these patients.
Because there is no specific treatment for Fragile-X syndrome, making a definitive diagnosis will
not lead to treatment that alters the natural history of the disorder. There are several potential
ways in which adjunctive management might be changed after confirmation of the diagnosis by
genetic testing. The American Academy of Pediatrics (AAP)5 and the American Academy of
Neurology (AAN) recommend cytogenetic evaluation in individuals with developmental delay to
look for certain chromosomal abnormalities that may be causally related to their condition. AAN
guidelines note that only in occasional cases will an etiologic diagnosis lead to specific therapy
that improves outcomes but suggest more immediate and general clinical benefits of achieving
a specific genetic diagnosis from the clinical viewpoint, as follows:

Limit additional diagnostic testing;

Anticipate and manage associated medical and behavioral comorbidities;

Improve understanding of treatment and prognosis; and

Allow counseling regarding risk of recurrence in future offspring and help with reproductive
planning.
AAP and AAN guidelines also emphasize the importance of early diagnosis and intervention in
an attempt to ameliorate or improve behavioral and cognitive outcomes over time. Guidelines
from AAP recommend against routine fragile X testing for children with isolated attentiondeficit/hyperactivity disorder.
Alpha-Thalassemia Preconception (Carrier) Testing
The major benefit of carrier testing is to define the likelihood of α-thalassemia major. Avoiding a
pregnancy with α-thalassemia major is of benefit in that a prospective mother will avoid carrying
a non-viable pregnancy, and will avoid the increased obstetrical complications associated with a
fetus with α-thalassemia major.
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Carrier screening with biochemical testing is recommended for all patients who are from an
ethnic groups with a high incidence of α-thalassemia. Biochemical screening consists of a CBC
with peripheral smear analysis. If there are any abnormalities noted, such as anemia,
microcytosis, or hypochromia, Hg electrophoresis is then performed to identify the specific types
of Hg present and between HgH disease. As noted, the hemoglobin electrophoresis may be
normal in the asymptomatic carrier and α-thalassemia trait states, but the states may be
suspected based on CBC and peripheral smear analysis.
Unlike for a clinical diagnosis, for carrier testing, it is important to distinguish between αthalassemia carrier (one abnormal gene) and α-thalassemia trait (two abnormal genes), and also
important to distinguish between the two variants of α-thalassemia trait, that is the aa/-- (cis
variant) and the a-/a- (trans variant). This is because only when both parents have the aa/-- cis
variant is there a risk for a fetus with α-thalassemia major.17 When both parents are αthalassemia carriers (aa/--), there is a 1 in 4 likelihood that an offspring will have α-thalassemia
major and hydrops fetalis. These parents may decide to pursue pre-implantation genetic
diagnosis in conjunction with in vitro fertilization to avoid a pregnancy with hydrops fetalis.
In this situation, genetic testing has incremental utility over biochemical testing. Whereas
biochemical testing can determine whether a silent carrier/trail syndrome is present, and can
distinguish those syndromes from HgH disease, it cannot provide a precise determination of the
number or pattern of abnormal alpha genes. As a result, using biochemical screening alone, the
probability of developing a hemoglobin Bart fetus cannot be accurately assessed. In contrast,
genetic testing can delineate the number of abnormal genes with certainty. In addition, genetic
testing can determine whether an α-thalassemia trait exists as the cis (aa/--) variant or the trans
(a-/a-) variant. Using this information from genetic testing, the probability of hemoglobin Bart
syndrome can be determined according to the table below.
Clinical Diagnosis in Genotype
Genotype
Probability of Hg Bart
Parents
(Parent 1)
(Parent 2)
Syndrome, %
Both parents silent carriers
aa/a-
aa/a-
0
One parent silent carrier, 1
aa/a-
a-/a-
0
aa/a--
0
aa/--
25
a-/a-
0
aa/--
0
a-/a-
0
parent trait
Both parents trait
aa/--
a-/a-
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One parent HgH, 1 parent
a-/--
aa/a-
0
a-/--
aa/--
25
a-/a-
0
a-/--
25
silent carrier
One parent HgH, 1 parent
trait
Both parents HgH
a-/--
Hg: hemoglobin
Parents can also determine the likelihood of HgH disease in an offspring through genetic
testing. However, because this is in most cases a mild condition, it is less likely to be considered
information that is actionable in terms of altering reproductive decision making.
Preconception (carrier) testing is likely to have clinical utility by providing incremental diagnostic
information over biochemical testing that can identify the pattern of abnormal alpha genes and
estimate more precisely the risk of hydrops fetalis.
Expanded Carrier Screening Panels
Expanded carrier screening (ECS) panels may provide the opportunity to test carriers for a
greatly expanded number of diseases for a lower cost than the conventional forms of carrier
testing. However, current limitations of these expanded panels include technical and interpretive
limitations and ethical and genetic counseling challenges, as outlined next.
In 2015, a joint statement on ECS was issued by ACMG, ACOG, the National Society of Genetic
Counselors, the Perinatal Quality Foundation and the Society for Maternal-Fetal Medicine.13 The
statement was not meant to replace current screening guidelines but to demonstrate an
approach for health care providers and laboratories that are seeking to or are currently offering
ECS panels. Some of the points to consider include the following:

ECS panels include most of the conditions recommended in current guidelines; however,
molecular methods used in ECS are not as accurate as methods recommended in current
guidelines for: the hemoglobinopathies, which require use of mean corpuscular volume and
hemoglobin electrophoresis, and for Tay-Sachs disease. The detection rate for Tay-Sachs
carrier status is low in non-Ashkenazi populations using molecular testing for the 3 common
Ashkenazi mutations-currently, hexoaminidase An enzyme analysis on blood is the best
method to identify carriers in all ethnicities.
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
Patients should be aware that newborn screening is mandated by all states and can identify
some of genetic conditions in the newborn. However, newborn screening may include a
different panel of conditions than ECS. Newborn screening does not usually detect children
who are carriers for the conditions being screened so will not necessarily identify carrier
parents at increased risk.

ECS can be performed by genotyping, which searches for known pathogenic and likely
pathogenic variants, or by DNA sequencing, which analyzes the entire coding region of the
gene and identifies alterations from the normal sequence. Genotyping includes selected
variants, but sequencing has the potential to identify benign and likely benign variants and
variants of unknown significance, in addition to pathogenic variants. Therefore, ECS panels
should only include genes and variants with a well-understood relationship with a
phenotype. When carrier frequency and detection rate are both known, residual risk
estimation should be provided in the lab report.

Conditions with unclear value on preconception and prenatal screening panels include
alpha-1-antitrypsin (A1AT), methylene tetrahydrofolate reductase (MTHFR) and hereditary
hemochromatosis (HH).
There is currently little evidence that addresses reproductive outcomes using ECS. Future
research needs in ECS should focus on data collection and development of a curated data
repository, and education of health care providers and patients. To improve the predictive value
of ECS, previously unreported and relatively rare variants and full phenotypes of homozygous
and compound heterozygotes should be collected and made available. Determining the
frequency of variants in previously untested ethnic and racial groups is required because risks
associated with gene variants may vary with different genetic backgrounds and in different
environmental situations. Collaborative analysis among laboratories is necessary to further
understanding of ECS.
A 2011 study by Bell et al., described the development of an ECS panel for 448 severe recessive
diseases of childhood, using next generation sequencing (NGS).14 The authors tested 104
unrelated DNA samples. They noted that although technical standards and guidelines for
laboratory-developed genetic testing for rare disorders in accredited laboratories have been
established, there are several challenges in their adoption for NGS and for bioinformatic-based
testing of many conditions. Specific national standards for quality assurance, quality control, test
accessioning and reporting, and proficiency evaluation does not currently exist. Also, issues of
specificity and false positives are complex when hundreds of genes are being sequenced
simultaneously and need to be addressed.
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Lazarin et al. (2013) reported on carrier status from an ethnically diverse clinical sample of
23,452 individuals.15 Using the Counsyl test screening platform, they assayed 417 diseasecausing mutations associated with 108 recessive diseases. Of the individuals tested, 5,633 (24%)
were heterozygous for at least one condition, and 5.2% were identified as carriers for multiple
disorders. Of 127 carrier couples identified (i.e., pairs of individuals identified as partners by selfreport who were both found to share heterozygosity for at least one disease), 47 (37%) were for
alpha-1 antitrypsin deficiency, a condition which has reduced penetrance, variable severity, and
uncertain clinical presentation in the newborn period and into adulthood. The American
Thoracic Society discourages genetic testing for alpha-1 antitrypsin deficiency in asymptomatic
adults with no increased risk for this disease.16
In March 2011, 6 U.S. academic centers convened focus groups to examine genetics
professionals’ views on ECS.17 Forty genetics professionals, including those specializing in
medical genetics, pediatric genetics, genetic counseling, public health genetics, primary care,
laboratory medicine, and law and bioethics, aimed to clarify how genetics professionals view
potential benefits and challenges of ECS. Overall, participants agreed that there was financial
value in ECS panels compared with conventional carrier screening. However, their findings
highlighted major limitations of ECS. Concerns included the following:

Use of ECS panels would be a significant departure from clinical practice guidelines in
genetic and reproductive healthcare in the United States, and carrier screening guidelines
currently exist for only a few of the genetic disorders evaluated by ECS panels.

Technical limitations of ECS include the inability to fully rule out the possibility of severe
recessive diseases due to rare mutations that could be identified by alternative methods
such as DNA sequencing, and, there are gaps in coverage of both specific genes and
individual mutations included in the ECS panels.

Current ECS panels typically examine only a fraction of the many genes associated with
genetic disorders and limit their evaluation to common genetic mutations within those
genes.

Reproductive healthcare providers might fail to recommend more conventional forms of
targeted genetic evaluation, such as screening tests indicated by a couple’s ethnicity, based
on erroneous perceptions about the coverage of ECS products being marketed as universal
in scope. Less common mutations in specific ethnic populations may not be included, and
couples may be falsely reassured by “negative” results.
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
As the number of individual assays on a multiplexed genetic test increases, the likelihood of
erroneous results (e.g., false positives) and clinically ambiguous findings (e.g., variants of
unknown significance) increases significantly.

As carrier screening panels expand to include less common genetic diseases, interpretation
of mutation results is hindered by lack of data on clinical phenotypes associated with rare
variants.
In 2013, Wienke et al. issued a commentary on the limitations of using ECS panels.18 The authors
stated that:

Patients may not understand the nature of every disease on the panel, confounding the
process of informed consent.

In practice, it is infeasible to inform patients of the nature of each condition tested, and
many healthcare providers are unfamiliar with some of the conditions tested, making it
difficult to communicate residual risk and take action on the information obtained.

Panels usually include diseases with decreased penetrance and variable expressivity that are
unlikely to be life-threatening in a patient with a negative family history (e.g., Factor V Leiden
thrombophilia, hemochromatosis, methylenetetrahydrofolate reductase [MTHFR] deficiency).
Screening for mutations that have unclear clinical significance has unclear implications in
reproductive decision making.

It is possible that a test primarily designed to assess reproductive risk will inadvertently
identify an asymptomatic individual with the disease, which poses many challenges. These
include unanticipated psychosocial burden to patients, and a burden to the healthcare
system in general as a person identified through this method may undergo additional
baseline testing for the disease and receive follow-up for the disease that may otherwise
have been unnecessary.
Genetic Counseling
Genetic counseling is primarily aimed at patients who are at risk for inherited disorders, and
experts recommend formal genetic counseling in most cases when genetic testing for an
inherited condition is considered. The Interpretation of the results of genetic tests and the
understanding of risk factors can be very difficult and complex. Therefore, genetic counseling
will assist individuals in understanding the possible benefits and harms of genetic testing,
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including the possible impact of the information on the individual’s family. Genetic counseling
may alter the utilization of genetic testing substantially and may reduce inappropriate testing.
Genetic counseling should be performed by an individual with experience and expertise in
genetic medicine and genetic testing methods.
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in the Table 1below.
Table 1: Summary of Key Trials
NCT No.
Trial Name
Planned
Completion
Enrollment
Date
400
May 2017
Ongoing
NCT01902901
Clinical Implementation of Carrier Status
Using Next Generation Sequencing
NCT: National Clinical Trial
Summary of Evidence
The evidence for carrier testing in individuals who are asymptomatic but at risk for having an
offspring with a genetic disease includes mutation prevalence studies, general principles of
carrier testing and accepted practice guidelines from major medical societies, which provides a
framework for evaluating these tests; direct evidence on outcomes with carrier testing is lacking.
Relevant outcomes are test accuracy, test validity and changes in reproductive decision making.
Reported analytic validity (technical accuracy) of targeted carrier screening tests is high. Changes
in management involve family planning decisions. Results of genetic testing can be used to
assist individuals with reproductive decisions such as avoidance of pregnancy, preimplantation
genetic testing, adoption, etc. Therefore, the evidence is sufficient to determine qualitatively that
the technology results in a meaningful improvement in the net health outcome.
The evidence for preconception (carrier) genetic testing for alpha-thalassemia includes case
reports and case series that correlate pathogenic mutations with clinical disease. Relevant
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outcomes are test accuracy, test validity, and changes in reproductive decision making.
Preconception carrier testing is intended to avoid the most serious form of α-thalassemia,
hemoglobin Bart disease. This condition leads to intrauterine death or death shortly after birth
and is associated with increased obstetrical risks for the mother. Screening of populations at risk
is first done by biochemical tests, including hemoglobin electrophoresis and complete blood
count and peripheral smear, but these tests cannot reliably distinguish between the carrier and
trait syndromes and cannot determine which configuration of mutations is present in αthalassemia trait. They therefore cannot completely determine the risk of a pregnancy with
hemoglobin Bart syndrome and hydrops fetalis. Genetic testing can determine with certainty the
number of abnormal genes present, and therefore can more precisely determine the risk of
hydrops fetalis. Therefore, the evidence is sufficient to determine qualitatively that the
technology results in a meaningful improvement in the net health outcome.
The evidence for FMR1 mutation testing (including Fragile X) in individuals with intellectual
disability, developmental delay, or autism spectrum disorder or in affected individuals or at-risk
relatives in whom testing will affect reproductive decision making includes studies evaluating
the analytic and clinical validity of FMR1 mutation testing and a chain of indirect evidence for
demonstration of clinical outcome improvements. Relevant outcomes are test accuracy, test
validity, resource utilization, and changes in reproductive decision making. Analytic sensitivity
and specificity for diagnosing these disorders has been demonstrated to be sufficiently high.
The evidence demonstrates that FMR1 mutation testing can establish a definitive diagnosis of
FXS when the test is positive for a pathogenic mutation. Following a definitive diagnosis, there
are a variety of ways management may change. Providing a diagnosis can eliminate the need for
further clinical workup. For certain mutations, results may aid in management of
psychopharmacologic interventions, assist in informed reproductive decision making, or both.
Although direct evidence for improved outcomes is insufficient, there is a chain of indirect
evidence that supports improvements in outcomes following FMR1 mutation testing. The
evidence is sufficient to determine qualitatively that the technology results in a meaningful
improvement in the net health outcome.
The evidence for expanded carrier testing in individuals who are asymptomatic but at risk for
having an offspring with a genetic disease includes mutation prevalence studies; direct evidence
is lacking. Relevant outcomes are test accuracy, test validity and changes in reproductive
decision making. analytic validity of expanded carrier screening (ECS) panels is unknown. ECS
panels have significant limitations, including increased false positives and variants of uncertain
significance due to testing for many mutations, false negatives due to rare mutations not
included in panel testing, the inclusion of diseases with decreased penetrance and variable
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expressivity that are unlikely to be life-threatening in a patient with a negative family history and
difficulties with communicating residual risk and actionability of information obtained.
Therefore, the evidence is insufficient to determine the effects of the technology on health
outcomes.
Practice Guidelines and Position Statements
Ethnic groups with a higher carrier rate for a particular condition.
Ashkenazi Jewish
In 2014, the American Congress of Obstetricians and Gynecologists (ACOG) reaffirmed a 2009
committee opinion that carrier screening for Tay-Sachs disease, Canavan disease, cystic fibrosis,
and familial dysautonomia should be offered to Ashkenazi Jewish individuals before conception
or during pregnancy so that a couple has an opportunity to consider prenatal diagnostic testing
options.4,5 The committee opinion stated that individuals of Ashkenazi Jewish descent may
inquire about the availability of carrier screening for other disorders found among individuals of
Eastern European Jewish descent, and that carrier screening is available for mucolipidosis IV,
Niemann-Pick disease type A, Fanconi anemia group C, Bloom syndrome, and Gaucher disease,
and that patient education materials can be made available so that interested patients can make
informed decisions about having additional screening tests. When only one partner is of
Ashkenazi Jewish descent, that individual should be screened first. If that individual is a carrier,
the other partner should be offered screening; however, the couple should be informed that
because carrier frequency and detection rate in non-Jewish individuals is unknown for all of
these disorders (except for Tay-Sachs disease and cystic fibrosis), it is difficult to predict the
couple’s risk of having a child with one of the disorders. If an individual has a positive family
history for one of these disorders, he or she should be offered carrier screening for that specific
disorder. When both partners are carriers of one of these disorders, they should be referred for
genetic counseling and offered prenatal diagnosis.
In 2013, The American College of Medical Genetics and Genomics (ACMG) reaffirmed a 2008
guideline that recommended carrier screening for cystic fibrosis, Canavan disease, familial
dysautonomia, and Tay-Sachs disease be offered to all individuals of Ashkenazi Jewish descent
who are pregnant, or considering pregnancy.2,3 ACMG also recommended that carrier screening
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be offered for Fanconi anemia (group C), Niemann-Pick (type A), Bloom syndrome,
mucolipidosis IV, and Gaucher disease.
According to ACMG, if only 1 member of the couple is Jewish, ideally, that individual should be
tested first. If the Jewish partner has a positive carrier test result, the other partner (regardless of
ethnic background) should be screened for that particular disorder. One Jewish grandparent is
sufficient to offer testing.
Hemoglobinopathies
Society of Obstetricians and Gynaecologists of Canada
The Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada
published guidelines on carrier testing for thalassemia in 2008. These guidelines included the
following recommendations:

Carrier screening for α-thalassemia should be offered to all woman from ethnic groups with
an increased prevalence of α-thalassemia. Initial screening should consist of CBC, Hg
electrophoresis (or hemoglobin high performance liquid chromatography), ferritin testing
and examination of peripheral smear for the presence of H bodies.

If a woman is found to have abnormal results on initial screen, testing of the partner should
be performed using the same battery of tests.

If both partners are found to be carriers of thalassemia, or combination of a thalassemia and
hemoglobin variant, they should be referred for genetic counseling. Additional molecular
studies may be required to clarify the carrier status of the parents and thus the risk to the
fetus.
In 2013, ACOG reaffirmed a 2007 guideline for hemoglobinopathies in pregnancy, which
included recommendations for carrier screening.6,7 For carrier screening, individuals of African,
Southeast Asian, and Mediterranean descent are at risk for being carriers of
hemoglobinopathies; ACOG recommended that individuals from these ethnic group should be
offered carrier screening and, if both parents are determined to be carriers, genetic counseling.
A complete blood count and hemoglobin electrophoresis are appropriate laboratory tests for
screening for hemoglobinopathies.
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Cystic Fibrosis
The initial ACMG Cystic Fibrosis Carrier Screening Working Group recommended that
laboratories use a pan-ethnic panel of 25 mutations present in at least 0.1% of patients with
classic cystic fibrosis (CF).19 Current guidelines, revised by ACMG in 2004 9 and reaffirmed in
2013,3 recommend a 23-mutation panel and were developed after assessing initial experiences
on implementation of CF screening into clinical practice. CF screening also may identify
5T/7T/9T variants in the CFTR gene, which vary between individuals. Genetic counseling is
important to discern whether the combination of mutations and variants would cause classic or
atypical CF.
Complete analysis of the CFTR gene by DNA sequencing is not appropriate for routine carrier
screening because it may yield results that can be difficult to interpret. This type of testing is
generally reserved for patients with CF, patients with a family history of CF, males with
congenital bilateral absence of the vas deferens, or newborns with a positive newborn screening
result when mutation testing, using the standard 23-mutation panel, has a negative result.
Because carrier screening detects most mutations, sequence analysis should be considered only
after discussion with a genetics professional to determine if sequencing will be informative after
standard screening has been performed.
In 2011, ACOG issued an update on carrier screening for CF, and the Committee on Genetics
provided the following guidelines8:

It is important that CF screening continue to be offered to women of reproductive age. It is
becoming increasingly difficult to assign a single ethnicity to individuals. It is reasonable,
therefore, to offer CF carrier screening to all patients. Screening is most efficacious in the
non-Hispanic white and Ashkenazi Jewish populations.

It is prudent to determine whether the patient has been previously screened before ordering
CF screening that may be redundant. If a patient has been screened previously, CF screening
results should be documented, but the test should not be repeated.

Complete analysis of the CFTR gene by DNA sequencing is not appropriate for routine
carrier screening.

Newborn screening panels that include CF screening do not replace maternal carrier
screening.
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
If a woman with CF wants to become pregnant, a multidisciplinary team should be consulted
to manage issues regarding pulmonary function, weight gain, infections, and increased risks
of diabetes and preterm delivery.

For couples in which both partners are carriers, genetic counseling is recommended to
review prenatal testing and reproductive options.

For couples in which both partners are unaffected but one or both has a family history of CF,
genetic counseling and medical record review should be performed to identify whether CFTR
mutation analysis in the affected family member is available.

If a woman's reproductive partner has CF or apparently isolated congenital bilateral absence
of the vas deferens, the couple should be referred to a genetics professional for mutation
analysis and consultation.
Spinal Muscular Atrophy
Current practice guidelines for spinal muscular atrophy (SMA) carrier testing from ACMG and
ACOG are in conflict. ACMG’s 2008 guideline, reaffirmed in 2013, recommends carrier testing for
SMA in all couples regardless of race or ethnicity.3,10 ACOG’s 2009 Committee on Genetics
opinion statement limits SMA carrier screening (1) to those with a family history of SMA or SMAlike disease, and (2) to those who request SMA carrier screening and have completed genetic
counseling to review sensitivity, specificity, and limitations of screening.11 The genetics of SMA
is complex, involving 2 genes; 95% of patients have a deletion in SMN1, but variable copy
number of SMN2 affects phenotypic expression (greater copy number is associated with milder
disease). Further, copy number of SMN1 can vary, confounding interpretation of a negative
(normal) result, e.g., 2 SMN1 copies on 1 chromosome may mask SMN1 deletion from the other
chromosome. Because of this complexity and residual risk with a negative result, ACOG opinion
authors recommended pilot studies to determine best practices for pre- and posttest education
and counseling before implementing pan-ethnic SMA carrier screening.
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FMR1 Mutations/Fragile X Syndrome
American College of Medical Genetics
American College of Medical Genetics’s (ACMG) Professional Practice and Guidelines Committee
makes the following recommendations regarding diagnostic and carrier testing for FXS. The
purpose of these recommendations is to provide general guidelines to aid clinicians in making
referrals for testing the repeat region of the FMR1 gene.

Individuals of either sex with intellectual disability, developmental delay, or autism, especially
if they have (a) any physical or behavioral characteristics of fragile X syndrome, (b) a family
history of fragile X syndrome, or (c) male or female relatives with undiagnosed intellectual
disability.

Individuals seeking reproductive counseling who have (a) a family history of fragile X
syndrome or (b) a family history of undiagnosed intellectual disability.

Fetuses of known carrier mothers.

Affected individuals or their relatives in the context of a positive cytogenetic fragile X test
result who are seeking further counseling related to the risk of carrier status among
themselves or their relatives. The cytogenetic test was used before the identification of the
FMR1 gene and is significantly less accurate than the current DNA test. DNA testing on such
individuals is warranted to accurately identify premutation carriers and to distinguish
premutation from full mutation carrier women.
In the clinical genetics evaluation to identify the etiology of autism spectrum disorders, ACMG
recommends testing for FXS as part of first tier testing.
Academy of Pediatrics
The Academy of Pediatrics recommends that, because children with FXS may not have apparent
physical features, any child who presents with developmental delay, borderline intellectual
abilities, or intellectual disability, or has a diagnosis of autism without a specific etiology should
undergo molecular testing for FXS to determine the number of CGG repeats.
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American Congress of Obstetricians and Gynecologists
The American Congress of Obstetricians and Gynecologists (Committee Opinion, 2010)
recommends that prenatal testing for FXS should be offered to known carriers of the fragile X
premutation or full mutation, and to women with a family history of fragile X‒related disorders,
unexplained intellectual disability or developmental delay, autism, or premature ovarian
insufficiency.
European Molecular Genetic Quality Network
In 2015, the European Molecular Genetic Quality Network issued best practice guidelines for the
molecular genetic testing and reporting of FXS, fragile X‒associated primary ovarian
insufficiency, and fragile X‒associated tremor/ataxia syndrome.20 The guidelines recommend “a
method which detects the whole range of expansions when testing relatives (including prenatal
diagnosis) in a family with any known fragile X disorder due to expansion.” Technical limitations
of specific techniques, such as Southern blot and PCR‒based methods, are described.
Expanded Panel Testing
In 2013, ACMG issued a position statement on prenatal/preconception expanded carrier
testing.1 For a particular disorder to be included in carrier screening, the following criteria should
be met:
1. Disorders should be of a nature that most at-risk patients and their partners identified in the
screening program would consider having a prenatal diagnosis to facilitate making decisions
surrounding reproduction.
a. The inclusion of disorders characterized by variable expressivity or incomplete
penetrance and those known to be associated with a mild phenotype should be optional
and made transparent when using these technologies for screening. This
recommendation is guided by the ethical principle of nonmaleficence.
2. When adult-onset disorders (disorders that could affect offspring of the individual
undergoing carrier screening once offspring reach adult life) are included in screening
panels, patients must provide consent to screening for these conditions, especially when
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there may be implications for the health of the individual being screened or for other family
members.
a. This recommendation follows the ethical principles of autonomy and nonmaleficence.
3. For each disorder, the causative gene(s), mutations, and mutation frequencies should be
known in the population being tested, so that meaningful residual risk in individuals who
test negative can be assessed.
a. Laboratories should specify in their marketing literature and test results how residual risk
was calculated using pan-ethnic population data or a specific race/ethnic group.
b. The calculation of residual risk requires knowledge of two factors: one is the carrier
frequency within a population, the other is the proportion of disease-causing alleles
detected using the specific testing platform. Laboratories using multiplex platforms often
have limited knowledge of one or both factors. Laboratories offering expanded carrier
screening should keep data prospectively and regularly report findings that allow
computation of residual risk estimates for all disorders being offered. When data are
inadequate, patient materials must stress that negative results should not be over
interpreted.
4. There must be validated clinical association between the mutation(s) detected and the
severity of the disorder.
a. Patient and provider materials must include specific citations that support inclusion of
the mutations for which screening is being performed.
5. ECS tests must comply with ACMG’s Standards and Guidelines for Clinical Genetics
Laboratories, including quality control and proficiency testing.
a. Quality control should include the entire test process, including preanalytical, analytical,
and postanalytical phases. Test performance characteristics should be available to
patients and providers accessing testing. A highly multiplexed approach will require a
more generic consent process than is typically used for single-disease screening because
it may be impractical for a clinician to discuss each disease included in a multidisease
carrier screening panel. An appropriately tailored informational pamphlet or web site,
containing a brief description of each disorder included in a test panel, should be
available to patients undergoing or considering an expanded prenatal/preconception
carrier screening panel. Genetic counseling before testing should be available to those
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who desire this, and posttest genetic counseling for those with positive screening results
is recommended.
U.S. Preventive Services Task Force Recommendations
The U.S. Preventive Services Task Force (USPSTF) makes recommendations for carrier testing for
BRCA-associated genetic diseases and for hereditary hemochromatosis, topics that are not
included in this policy but in separate policies for each condition.
Medicare National Coverage
There is no national coverage determination (NCD). In the absence of an NCD, coverage
decisions are left to the discretion of local Medicare carriers.
Regulatory Status
Clinical laboratories may develop and validate tests in-house and market them as a laboratory
service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the
Clinical Laboratory Improvement Act (CLIA). Laboratories that offer LDTs must be licensed by
CLIA for high-complexity testing.
There are a number of commercially available genetic tests for carrier screening, which range
from testing for individual diseases, to small panels designed to address testing based on
ethnicity as recommended by practice guidelines (American College of Obstetricians and
Gynecologists [ACOG], American College of Medical Genetics and Genomics [ACMG]), to large
expanded panels that test for numerous diseases beyond those recommended in practice
guidelines. The following is not a comprehensive list of some of the available panels:

Counsyl™ (Counsyl): Tests for more than 100 diseases, which, according to the
manufacturer website, lead to shortened lifespan, have limited treatment or can lead to
intellectual disability. Diseases tested for include those recommended by ACOG, ACMG, as
well as an Ashkenazi Jewish panel, Fragile-X syndrome, a 100-mutation CF panel, sickle cell
disease, and metabolic disorders.

GoodStart Select™ (GoodStart Genetics): “Customizes” the testing panel for each patient
based on ethnicity, family history, and provider testing preferences. The test menu includes
Page | 26 of 30
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several ethnic panels, and includes testing for hemoglobinopathies, Fragile-X syndrome, CF,
metabolic disorders, and others.

Inherigen™ (GenPath): A pan-ethnic test for over 160 inherited disorders, typically those
with childhood onset and severe symptoms, such as immunodeficiencies and several
metabolic diseases, such as Tay-Sachs disease, glycogen storage diseases, and fatty acid
oxidation disorders. InheriGen Plus includes all InheriGen diseases plus CF, SMA, and FragileX syndrome.

Inheritest™ (LabCorp): A pan-ethnic test for more than 90 autosomal recessive inherited
diseases. The Inheritest Select Carrier Screen is a test that evaluates diseases for patients of
Ashkenazi Jewish descent.

Natera One™ Disease Panel (Natera): Tests for 13 diseases, which include ACMGrecommended tests for carrier screening, plus Fragile-X syndrome, sickle cell anemia,
hemoglobin C trait, and SMA.
Natera Horizon has 5 different panels that screen for as few as 4 and up to 274 autosomal and
X-linked genetic conditions. The panels are pan-ethnic, ancestry-based or expanded.
Two CLIA-certified laboratories, Progenity™ (Ann Arbor, Michigan; formerly aMDx Laboratory
Sciences and Ascendant MDx) and Sequenom® Laboratories (San Diego, CA), offer both single
disease carrier testing (cystic fibrosis [CFnxt cystic fibrosis and HerediT™ Cystic Fibrosis Carrier
Screen, respectively], fragile X syndrome [Fragile X syndrome and HerediT™ Cystic Fibrosis
Carrier Screen, respectively], SMA [SMAnxt spinal muscular atrophy and HerediT™ Spinal
Muscular Atrophy Carrier Screen, respectively) and disease panels for Ashkenazi Jewish patients
(AJPnxt Basic [9 diseases] or AJPnxt Expanded [19 diseases] and HerediT™ Ashkenazi Jewish
Panel Carrier Screen [17 diseases], respectively). Progenity™ also offers nxtPanel for
simultaneous CF, SMA, and fragile X syndrome testing.
References
1.
Grody WW, Thompson BH, Gregg AR, et al. ACMG position statement on prenatal/preconception expanded carrier screening.
Genet Med. Jun 2013; 15(6):482-483. PMID 23619275
2.
Gross SJ, Pletcher BA, Monaghan KG. Carrier screening in individuals of Ashkenazi Jewish descent. Genet Med. Jan
2008;10(1):54-56. PMID 18197057
Page | 27 of 30
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3.
American College of Medical Genetics and Genomics Practice Guidelines.
https://www.acmg.net/ACMG/Publications/Practice_Guidelines/ACMG/Publications/Practice_Guidelines.aspx?hkey=b5
e361a3-65b1-40ae-bb3e-4254fce9453a. Accessed April 2016.
4.
ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern
European Jewish descent. Obstet Gynecol. Oct 2009;114(4):950-953. PMID 19888064
5.
American Congress of Obstetricians and Gynecologists Committee Opinions. http://www.acog.org/Resources-AndPublications/Committee-Opinions-List. Accessed April 2016.
6.
American Family Physician. Practice guidelines on heomglobinopathies in pregnancy. 2007;
http://www.aafp.org/afp/2007/1015/p1229.html. Accessed April 2016.
7.
ACOG. Practice bulletin number 78: hemoglobinopathies in pregnancy, January 2007; reaffirmed 2013.
http://www.acog.org/Search?Keyword=hemoglobinopathy. Accessed April 2016.
8.
ACOG Committee Opinion No. 486: Update on carrier screening for cystic fibrosis. Obstet Gynecol. Apr 2011;117(4):1028-1031.
PMID 21422883
9.
Watson MS, Cutting GR, Desnick RJ, et al. Cystic fibrosis population carrier screening: 2004 revision of American College of
Medical Genetics mutation panel. Genet Med. Sep-Oct 2004;6(5):387-391. PMID 15371902
10. Prior TW. Carrier screening for spinal muscular atrophy. Genet Med. Nov 2008;10(11):840-842. PMID 18941424
11. ACOG Committee Opinion No. 432: spinal muscular atrophy. Obstet Gynecol. May 2009;113(5):1194-1196. PMID 19384151
12. Arup Laboratories. Ashkenazi Jewish diseases, common mutation panel. http://ltd.aruplab.com/tests/pub/0051415.
Accessed April 2016.
13. Edwards JG, Feldman G, Goldberg J, et al. Expanded carrier screening in reproductive medicine-points to consider: a joint
statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists,
National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine. Obstet Gynecol.
Mar 2015;125(3):653-662. PMID 25730230
14. Bell CJ, Dinwiddie DL, Miller NA, et al. Carrier testing for severe childhood recessive diseases by next -generation sequencing.
Sci Transl Med. Jan 12 2011; 3(65):65ra64. PMID 21228398
15. Lazarin GA, Haque IS, Nazareth S, et al. An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results
from an ethnically diverse clinical sample of 23,453 individuals. Genet Med. Mar 2013; 15(3):178-186. PMID 22975760
16. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals
with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. Oct 1 2003; 168(7):818-900. PMID 14522813
17. Cho D, McGowan ML, Metcalfe J, et al. Expanded carrier screening in reproductive healthcare: perspectives from genetics
professionals. Hum Reprod. Jun 2013; 28(6):1725-1730. PMID 23589535
18. Wienke S, Brown K, Farmer M, et al. Expanded carrier screening panels-does bigger mean better? J Community Genet. Sep 24
2013. PMID 24062228
19. Grody WW, Cutting GR, Klinger KW, et al. Laboratory standards and guidelines for population-based cystic fibrosis carrier
screening. Genet Med. Mar-Apr 2001;3(2):149-154. PMID 11280952
20. Muncie HL, Jr., Campbell J. Alpha and beta thalassemia. Am Fam Physician. Aug 15 2009; 80(4):339-344. PMID 19678601
21. Galanello R, Cao A. Gene test review. Alpha-thalassemia. Genet Med. Feb 2011; 13(2):83-88. PMID 21381239
22. Vichinsky E. Complexity of alpha thalassemia: growing health problem with new approaches to screening, diagnosis, and
therapy. Ann N Y Acad Sci. Aug 2010; 1202:180-187. PMID 20712791
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23. Origa R, Moi P, Galanello R, et al. Alpha-Thalassemia. GeneReviews 2005; http://www.ncbi.nlm.nih.gov/books/NBK1435/.
PMID 20301608. Accessed April 2016.
24. Langlois S, Ford JC, Chitayat D, et al. Carrier screening for thalassemia and hemoglobinopathies in Canada. J Obstet Gynaecol
Can. Oct 2008; 30(10):950-971. PMID 19038079
25. Schaefer GB, Mendelsohn NJ. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013
guideline revisions. Genet Med. May 2013;15(5):399-407. PMID 23519317
26. Miles JH. Autism spectrum disorders--a genetics review. Genet Med. Apr 2011;13(4):278-294. PMID 21358411
27. Hersh JH, Saul RA. Health supervision for children with fragile X syndrome. Pediatrics. May 2011;127(5):994-1006. PMID
21518720
28. Sherman S, Pletcher BA, Driscoll DA. Fragile X syndrome: diagnostic and carrier testing. Genet Med. Oct 2005;7(8):584-587.
PMID 16247297
29. Michelson DJ, Shevell MI, Sherr EH, et al. Evidence report: Genetic and metabolic testing on children with global developmental
delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of
the Child Neurology Society. Neurology. Oct 25 2011;77(17):1629-1635. PMID 21956720
30. Subcommittee on Attention-Deficit/Hyperactivity Disorder SCoQI, Management. ADHD: Clinical Guideline for the Diagnosis,
Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics. November 1,
2011; 128(5):1007-1022. PMID
31. American Congress of Obstetricians and Gynecologis (ACOG). Committee opinion number 469: Carrier Screening for Fragine X
Syndrome. 2010.
http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Genetics/Carrier_Screening_for
_Fragile_X_Syndrome. Accessed April 4, 2016.
32. Biancalana V, Glaeser D, McQuaid S, et al. EMQN best practice guidelines for the molecular genetic testing and reporting of
fragile X syndrome and other fragile X-associated disorders. Eur J Hum Genet. Apr 2015;23(4):417-425. PMID 25227148
33. Blue Cross Blue Shield Association MPRM 2.04.83 Genetic Testing for FMR1 Mutations (Including Fragile X Syndrome). Last
accessed March 5, 2016.
History
Date
Comments
01/12/16
Annual review. Policy renumbered, replaces 12.04.107. Policy updated with literature
review through August 31, 2015. Policy statement on personal/family history criteria
consolidated to eliminate redundancies. Policy statement and Guidelines amended to
include necessity statements on specific carrier tests – cystic fibrosis, spinal muscular
atrophy, Ashkenazi Jewish Panel, hemoglobinopathies. Definitions of 1st, 2nd and 3rd
degree relatives added. Reference added.
05/01/16
Interim update, approved April 12, 2016. Genetic Testing for Alpha-Thalassemia
incorporated into this policy for ease of use. New policy statement added: Fragile-X
Syndrome testing may be considered medically necessary when criteria are met.
Page | 29 of 30
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Date
Comments
07/01/16
Policy moved to new format. No change in content or coverage.
08/01/16
Interim Update, approved July 12, 2016. Policy statement on genetic testing for FMR1
mutations changed from investigational to not medically necessary. Policy statements
of not medically necessary added to testing for Ashkenazi Jewish Founder and Other
Inherited Disorders when criteria are not met.
Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The
Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and
local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review
and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit
booklet or contact a member service representative to determine coverage for a specific medical service or supply.
CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA). ©2016 Premera
All Rights Reserved.
Scope: Medical policies are systematically developed guidelines that serve as a resource for Company staff when
determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to
the limits and conditions of the member benefit plan. Members and their providers should consult the member
benefit booklet or contact a customer service representative to determine whether there are any benefit limitations
applicable to this service or supply. This medical policy does not apply to Medicare Advantage.
Page | 30 of 30
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Discrimination is Against the Law
Premera Blue Cross complies with applicable Federal civil rights laws and
does not discriminate on the basis of race, color, national origin, age,
disability, or sex. Premera does not exclude people or treat them differently
because of race, color, national origin, age, disability or sex.
Premera:
• Provides free aids and services to people with disabilities to communicate
effectively with us, such as:
• Qualified sign language interpreters
• Written information in other formats (large print, audio, accessible
electronic formats, other formats)
• Provides free language services to people whose primary language is not
English, such as:
• Qualified interpreters
• Information written in other languages
If you need these services, contact the Civil Rights Coordinator.
If you believe that Premera has failed to provide these services or
discriminated in another way on the basis of race, color, national origin, age,
disability, or sex, you can file a grievance with:
Civil Rights Coordinator - Complaints and Appeals
PO Box 91102, Seattle, WA 98111
Toll free 855-332-4535, Fax 425-918-5592, TTY 800-842-5357
Email [email protected]
You can file a grievance in person or by mail, fax, or email. If you need help
filing a grievance, the Civil Rights Coordinator is available to help you.
You can also file a civil rights complaint with the U.S. Department of Health
and Human Services, Office for Civil Rights, electronically through the
Office for Civil Rights Complaint Portal, available at
https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:
U.S. Department of Health and Human Services
200 Independence Avenue SW, Room 509F, HHH Building
Washington, D.C. 20201, 1-800-368-1019, 800-537-7697 (TDD)
Complaint forms are available at
http://www.hhs.gov/ocr/office/file/index.html.
Getting Help in Other Languages
This Notice has Important Information. This notice may have important
information about your application or coverage through Premera Blue
Cross. There may be key dates in this notice. You may need to take action
by certain deadlines to keep your health coverage or help with costs. You
have the right to get this information and help in your language at no cost.
Call 800-722-1471 (TTY: 800-842-5357).
አማሪኛ (Amharic):
ይህ ማስታወቂያ አስፈላጊ መረጃ ይዟል። ይህ ማስታወቂያ ስለ ማመልከቻዎ ወይም የ Premera Blue
Cross ሽፋን አስፈላጊ መረጃ ሊኖረው ይችላል። በዚህ ማስታወቂያ ውስጥ ቁልፍ ቀኖች ሊኖሩ ይችላሉ።
የጤናን ሽፋንዎን ለመጠበቅና በአከፋፈል እርዳታ ለማግኘት በተውሰኑ የጊዜ ገደቦች እርምጃ መውሰድ
ይገባዎት ይሆናል። ይህን መረጃ እንዲያገኙ እና ያለምንም ክፍያ በቋንቋዎ እርዳታ እንዲያገኙ መብት
አለዎት።በስልክ ቁጥር 800-722-1471 (TTY: 800-842-5357) ይደውሉ።
‫( العربية‬Arabic):
‫ قد يحوي ھذا اإلشعار معلومات مھمة بخصوص طلبك أو‬.‫يحوي ھذا اإلشعار معلومات ھامة‬
‫ قد تكون ھناك تواريخ مھمة‬.Premera Blue Cross ‫التغطية التي تريد الحصول عليھا من خالل‬
‫ وقد تحتاج التخاذ إجراء في تواريخ معينة للحفاظ على تغطيتك الصحية أو للمساعدة‬.‫في ھذا اإلشعار‬
‫ اتصل‬.‫ يحق لك الحصول على ھذه المعلومات والمساعدة بلغتك دون تكبد أية تكلفة‬.‫في دفع التكاليف‬
800-722-1471 (TTY: 800-842-5357)‫بـ‬
中文 (Chinese):
本通知有重要的訊息。本通知可能有關於您透過 Premera Blue Cross 提交的
申請或保險的重要訊息。本通知內可能有重要日期。您可能需要在截止日期
之前採取行動，以保留您的健康保險或者費用補貼。您有權利免費以您的母
語得到本訊息和幫助。請撥電話 800-722-1471 (TTY: 800-842-5357)。
037338 (07-2016)
Oromoo (Cushite):
Beeksisni kun odeeffannoo barbaachisaa qaba. Beeksisti kun sagantaa
yookan karaa Premera Blue Cross tiin tajaajila keessan ilaalchisee
odeeffannoo barbaachisaa qabaachuu danda’a. Guyyaawwan murteessaa
ta’an beeksisa kana keessatti ilaalaa. Tarii kaffaltiidhaan deeggaramuuf
yookan tajaajila fayyaa keessaniif guyyaa dhumaa irratti wanti raawwattan
jiraachuu danda’a. Kaffaltii irraa bilisa haala ta’een afaan keessaniin
odeeffannoo argachuu fi deeggarsa argachuuf mirga ni qabaattu.
Lakkoofsa bilbilaa 800-722-1471 (TTY: 800-842-5357) tii bilbilaa.
Français (French):
Cet avis a d'importantes informations. Cet avis peut avoir d'importantes
informations sur votre demande ou la couverture par l'intermédiaire de
Premera Blue Cross. Le présent avis peut contenir des dates clés. Vous
devrez peut-être prendre des mesures par certains délais pour maintenir
votre couverture de santé ou d'aide avec les coûts. Vous avez le droit
d'obtenir cette information et de l’aide dans votre langue à aucun coût.
Appelez le 800-722-1471 (TTY: 800-842-5357).
Kreyòl ayisyen (Creole):
Avi sila a gen Enfòmasyon Enpòtan ladann. Avi sila a kapab genyen
enfòmasyon enpòtan konsènan aplikasyon w lan oswa konsènan kouvèti
asirans lan atravè Premera Blue Cross. Kapab genyen dat ki enpòtan nan
avi sila a. Ou ka gen pou pran kèk aksyon avan sèten dat limit pou ka
kenbe kouvèti asirans sante w la oswa pou yo ka ede w avèk depans yo.
Se dwa w pou resevwa enfòmasyon sa a ak asistans nan lang ou pale a,
san ou pa gen pou peye pou sa. Rele nan 800-722-1471
(TTY: 800-842-5357).
Deutsche (German):
Diese Benachrichtigung enthält wichtige Informationen. Diese
Benachrichtigung enthält unter Umständen wichtige Informationen
bezüglich Ihres Antrags auf Krankenversicherungsschutz durch Premera
Blue Cross. Suchen Sie nach eventuellen wichtigen Terminen in dieser
Benachrichtigung. Sie könnten bis zu bestimmten Stichtagen handeln
müssen, um Ihren Krankenversicherungsschutz oder Hilfe mit den Kosten
zu behalten. Sie haben das Recht, kostenlose Hilfe und Informationen in
Ihrer Sprache zu erhalten. Rufen Sie an unter 800-722-1471
(TTY: 800-842-5357).
Hmoob (Hmong):
Tsab ntawv tshaj xo no muaj cov ntshiab lus tseem ceeb. Tej zaum
tsab ntawv tshaj xo no muaj cov ntsiab lus tseem ceeb txog koj daim ntawv
thov kev pab los yog koj qhov kev pab cuam los ntawm Premera Blue
Cross. Tej zaum muaj cov hnub tseem ceeb uas sau rau hauv daim ntawv
no. Tej zaum koj kuj yuav tau ua qee yam uas peb kom koj ua tsis pub
dhau cov caij nyoog uas teev tseg rau hauv daim ntawv no mas koj thiaj
yuav tau txais kev pab cuam kho mob los yog kev pab them tej nqi kho mob
ntawd. Koj muaj cai kom lawv muab cov ntshiab lus no uas tau muab sau
ua koj hom lus pub dawb rau koj. Hu rau 800-722-1471
(TTY: 800-842-5357).
Iloko (Ilocano):
Daytoy a Pakdaar ket naglaon iti Napateg nga Impormasion. Daytoy a
pakdaar mabalin nga adda ket naglaon iti napateg nga impormasion
maipanggep iti apliksayonyo wenno coverage babaen iti Premera Blue
Cross. Daytoy ket mabalin dagiti importante a petsa iti daytoy a pakdaar.
Mabalin nga adda rumbeng nga aramidenyo nga addang sakbay dagiti
partikular a naituding nga aldaw tapno mapagtalinaedyo ti coverage ti
salun-atyo wenno tulong kadagiti gastos. Adda karbenganyo a mangala iti
daytoy nga impormasion ken tulong iti bukodyo a pagsasao nga awan ti
bayadanyo. Tumawag iti numero nga 800-722-1471 (TTY: 800-842-5357).
Italiano (Italian):
Questo avviso contiene informazioni importanti. Questo avviso può contenere
informazioni importanti sulla tua domanda o copertura attraverso Premera
Blue Cross. Potrebbero esserci date chiave in questo avviso. Potrebbe
essere necessario un tuo intervento entro una scadenza determinata per
consentirti di mantenere la tua copertura o sovvenzione. Hai il diritto di
ottenere queste informazioni e assistenza nella tua lingua gratuitamente.
Chiama 800-722-1471 (TTY: 800-842-5357).
日本語 (Japanese):
この通知には重要な情報が含まれています。この通知には、Premera Blue
Cross の申請または補償範囲に関する重要な情報が含まれている場合があ
ります。この通知に記載されている可能性がある重要な日付をご確認くだ
さい。健康保険や有料サポートを維持するには、特定の期日までに行動を
取らなければならない場合があります。ご希望の言語による情報とサポー
トが無料で提供されます。800-722-1471 (TTY: 800-842-5357)までお電話
ください。
Română (Romanian):
Prezenta notificare conține informații importante. Această notificare
poate conține informații importante privind cererea sau acoperirea asigurării
dumneavoastre de sănătate prin Premera Blue Cross. Pot exista date cheie
în această notificare. Este posibil să fie nevoie să acționați până la anumite
termene limită pentru a vă menține acoperirea asigurării de sănătate sau
asistența privitoare la costuri. Aveți dreptul de a obține gratuit aceste
informații și ajutor în limba dumneavoastră. Sunați la 800-722-1471
(TTY: 800-842-5357).
한국어 (Korean):
본 통지서에는 중요한 정보가 들어 있습니다. 즉 이 통지서는 귀하의 신청에
관하여 그리고 Premera Blue Cross 를 통한 커버리지에 관한 정보를
포함하고 있을 수 있습니다. 본 통지서에는 핵심이 되는 날짜들이 있을 수
있습니다. 귀하는 귀하의 건강 커버리지를 계속 유지하거나 비용을 절감하기
위해서 일정한 마감일까지 조치를 취해야 할 필요가 있을 수 있습니다.
귀하는 이러한 정보와 도움을 귀하의 언어로 비용 부담없이 얻을 수 있는
권리가 있습니다. 800-722-1471 (TTY: 800-842-5357) 로 전화하십시오.
Pусский (Russian):
Настоящее уведомление содержит важную информацию. Это
уведомление может содержать важную информацию о вашем
заявлении или страховом покрытии через Premera Blue Cross. В
настоящем уведомлении могут быть указаны ключевые даты. Вам,
возможно, потребуется принять меры к определенным предельным
срокам для сохранения страхового покрытия или помощи с расходами.
Вы имеете право на бесплатное получение этой информации и
помощь на вашем языке. Звоните по телефону 800-722-1471
(TTY: 800-842-5357).
ລາວ (Lao):
ແຈ້ ງການນ້ີ ມີຂ້ໍ ມູ ນສໍາຄັ ນ. ແຈ້ ງການນ້ີ ອາດຈະມີຂ້ໍ ມູ ນສໍາຄັ ນກ່ ຽວກັ ບຄໍາຮ້ ອງສະ
ໝັ ກ ຫື ຼ ຄວາມຄຸ້ ມຄອງປະກັ ນໄພຂອງທ່ ານຜ່ ານ Premera Blue Cross. ອາດຈະມີ
ວັ ນທີສໍາຄັ ນໃນແຈ້ ງການນີ້. ທ່ ານອາດຈະຈໍາເປັນຕ້ ອງດໍາເນີນການຕາມກໍານົ ດ
ເວລາສະເພາະເພື່ອຮັ ກສາຄວາມຄຸ້ ມຄອງປະກັ ນສຸ ຂະພາບ ຫື ຼ ຄວາມຊ່ ວຍເຫື ຼ ອເລື່ອງ
ຄ່ າໃຊ້ ຈ່ າຍຂອງທ່ ານໄວ້ . ທ່ ານມີສິດໄດ້ ຮັ ບຂ້ໍ ມູ ນນ້ີ ແລະ ຄວາມຊ່ ວຍເຫື ຼ ອເປັນພາສາ
ຂອງທ່ ານໂດຍບໍ່ເສຍຄ່ າ. ໃຫ້ ໂທຫາ 800-722-1471 (TTY: 800-842-5357).
ភាសាែខម រ (Khmer):
េសចកត ីជូនដំណឹងេនះមានព័ត៌មានយា៉ងសំខាន់។ េសចកត ីជូនដំណឹងេនះរបែហល
ជាមានព័ត៌មានយា៉ងសំខាន់អំពីទរមង់ែបបបទ ឬការរា៉ប់រងរបស់អនកតាមរយៈ
Premera Blue Cross ។ របែហលជាមាន កាលបរ ិេចឆ ទសំខាន់េនៅកនុងេសចកត ីជូន
ដំណឹងេនះ។ អន ករបែហលជារតូវការបេញច ញសមតថ ភាព ដល់កំណត់ៃថង ជាក់ចបាស់
នានា េដើមបីនឹងរកសាទុកការធានារា៉ប់រងសុខភាពរបស់អនក ឬរបាក់ជំនួយេចញៃថល ។
អន កមានសិទធិទទួ លព័ត៌មានេនះ និងជំនួយេនៅកនុងភាសារបស់អនកេដាយមិនអស
លុយេឡើយ។ សូ មទូ រស័ពទ 800-722-1471 (TTY: 800-842-5357)។
ਪੰ ਜਾਬੀ (Punjabi):
ਇਸ ਨੋਿਟਸ ਿਵਚ ਖਾਸ ਜਾਣਕਾਰੀ ਹੈ. ਇਸ ਨੋਿਟਸ ਿਵਚ Premera Blue Cross ਵਲ ਤੁਹਾਡੀ
ਕਵਰੇਜ ਅਤੇ ਅਰਜੀ ਬਾਰੇ ਮਹੱ ਤਵਪੂਰਨ ਜਾਣਕਾਰੀ ਹੋ ਸਕਦੀ ਹੈ . ਇਸ ਨੋਿਜਸ ਜਵਚ ਖਾਸ ਤਾਰੀਖਾ
ਹੋ ਸਕਦੀਆਂ ਹਨ. ਜੇਕਰ ਤੁਸੀ ਜਸਹਤ ਕਵਰੇਜ ਿਰੱ ਖਣੀ ਹੋਵੇ ਜਾ ਓਸ ਦੀ ਲਾਗਤ ਜਿਵੱ ਚ ਮਦਦ ਦੇ
ਇਛੁੱ ਕ ਹੋ ਤਾਂ ਤੁਹਾਨੂੰ ਅੰ ਤਮ ਤਾਰੀਖ਼ ਤ ਪਿਹਲਾਂ ਕੁੱ ਝ ਖਾਸ ਕਦਮ ਚੁੱ ਕਣ ਦੀ ਲੋ ੜ ਹੋ ਸਕਦੀ ਹੈ ,ਤੁਹਾਨੂੰ
ਮੁਫ਼ਤ ਿਵੱ ਚ ਤੇ ਆਪਣੀ ਭਾਸ਼ਾ ਿਵੱ ਚ ਜਾਣਕਾਰੀ ਅਤੇ ਮਦਦ ਪ੍ਰਾਪਤ ਕਰਨ ਦਾ ਅਿਧਕਾਰ ਹੈ ,ਕਾਲ
800-722-1471 (TTY: 800-842-5357).
‫( فارسی‬Farsi):
‫اين اعالميه ممکن است حاوی اطالعات مھم درباره فرم‬. ‫اين اعالميه حاوی اطالعات مھم ميباشد‬
‫ به تاريخ ھای مھم در‬.‫ باشد‬Premera Blue Cross ‫تقاضا و يا پوشش بيمه ای شما از طريق‬
‫شما ممکن است برای حقظ پوشش بيمه تان يا کمک در پرداخت ھزينه‬. ‫اين اعالميه توجه نماييد‬
‫شما حق‬. ‫ به تاريخ ھای مشخصی برای انجام کارھای خاصی احتياج داشته باشيد‬،‫ھای درمانی تان‬
‫ برای کسب‬.‫اين را داريد که اين اطالعات و کمک را به زبان خود به طور رايگان دريافت نماييد‬
‫( تماس‬800-842-5357 ‫ تماس باشماره‬TTY ‫ )کاربران‬800-722-1471 ‫اطالعات با شماره‬
.‫برقرار نماييد‬
Polskie (Polish):
To ogłoszenie może zawierać ważne informacje. To ogłoszenie może
zawierać ważne informacje odnośnie Państwa wniosku lub zakresu
świadczeń poprzez Premera Blue Cross. Prosimy zwrócic uwagę na
kluczowe daty, które mogą być zawarte w tym ogłoszeniu aby nie
przekroczyć terminów w przypadku utrzymania polisy ubezpieczeniowej lub
pomocy związanej z kosztami. Macie Państwo prawo do bezpłatnej
informacji we własnym języku. Zadzwońcie pod 800-722-1471
(TTY: 800-842-5357).
Português (Portuguese):
Este aviso contém informações importantes. Este aviso poderá conter
informações importantes a respeito de sua aplicação ou cobertura por meio
do Premera Blue Cross. Poderão existir datas importantes neste aviso.
Talvez seja necessário que você tome providências dentro de
determinados prazos para manter sua cobertura de saúde ou ajuda de
custos. Você tem o direito de obter esta informação e ajuda em seu idioma
e sem custos. Ligue para 800-722-1471 (TTY: 800-842-5357).
Fa’asamoa (Samoan):
Atonu ua iai i lenei fa’asilasilaga ni fa’amatalaga e sili ona taua e tatau
ona e malamalama i ai. O lenei fa’asilasilaga o se fesoasoani e fa’amatala
atili i ai i le tulaga o le polokalame, Premera Blue Cross, ua e tau fia maua
atu i ai. Fa’amolemole, ia e iloilo fa’alelei i aso fa’apitoa olo’o iai i lenei
fa’asilasilaga taua. Masalo o le’a iai ni feau e tatau ona e faia ao le’i aulia le
aso ua ta’ua i lenei fa’asilasilaga ina ia e iai pea ma maua fesoasoani mai ai
i le polokalame a le Malo olo’o e iai i ai. Olo’o iai iate oe le aia tatau e maua
atu i lenei fa’asilasilaga ma lenei fa’matalaga i legagana e te malamalama i
ai aunoa ma se togiga tupe. Vili atu i le telefoni 800-722-1471
(TTY: 800-842-5357).
Español (Spanish):
Este Aviso contiene información importante. Es posible que este aviso
contenga información importante acerca de su solicitud o cobertura a
través de Premera Blue Cross. Es posible que haya fechas clave en este
aviso. Es posible que deba tomar alguna medida antes de determinadas
fechas para mantener su cobertura médica o ayuda con los costos. Usted
tiene derecho a recibir esta información y ayuda en su idioma sin costo
alguno. Llame al 800-722-1471 (TTY: 800-842-5357).
Tagalog (Tagalog):
Ang Paunawa na ito ay naglalaman ng mahalagang impormasyon. Ang
paunawa na ito ay maaaring naglalaman ng mahalagang impormasyon
tungkol sa iyong aplikasyon o pagsakop sa pamamagitan ng Premera Blue
Cross. Maaaring may mga mahalagang petsa dito sa paunawa. Maaring
mangailangan ka na magsagawa ng hakbang sa ilang mga itinakdang
panahon upang mapanatili ang iyong pagsakop sa kalusugan o tulong na
walang gastos. May karapatan ka na makakuha ng ganitong impormasyon
at tulong sa iyong wika ng walang gastos. Tumawag sa 800-722-1471
(TTY: 800-842-5357).
ไทย (Thai):
ประกาศนี ้มีข้อมูลสําคัญ ประกาศนี ้อาจมีข้อมูลที่สําคัญเกี่ยวกับการการสมัครหรื อขอบเขตประกัน
สุขภาพของคุณผ่าน Premera Blue Cross และอาจมีกําหนดการในประกาศนี ้ คุณอาจจะต้ อง
ดําเนินการภายในกําหนดระยะเวลาที่แน่นอนเพื่อจะรักษาการประกันสุขภาพของคุณหรื อการช่วยเหลือที่
มีค่าใช้ จ่าย คุณมีสิทธิที่จะได้ รับข้ อมูลและความช่วยเหลือนี ้ในภาษาของคุณโดยไม่มีค่าใช้ จ่าย โทร
800-722-1471 (TTY: 800-842-5357)
Український (Ukrainian):
Це повідомлення містить важливу інформацію. Це повідомлення
може містити важливу інформацію про Ваше звернення щодо
страхувального покриття через Premera Blue Cross. Зверніть увагу на
ключові дати, які можуть бути вказані у цьому повідомленні. Існує
імовірність того, що Вам треба буде здійснити певні кроки у конкретні
кінцеві строки для того, щоб зберегти Ваше медичне страхування або
отримати фінансову допомогу. У Вас є право на отримання цієї
інформації та допомоги безкоштовно на Вашій рідній мові. Дзвоніть за
номером телефону 800-722-1471 (TTY: 800-842-5357).
Tiếng Việt (Vietnamese):
Thông báo này cung cấp thông tin quan trọng. Thông báo này có thông
tin quan trọng về đơn xin tham gia hoặc hợp đồng bảo hiểm của quý vị qua
chương trình Premera Blue Cross. Xin xem ngày quan trọng trong thông
báo này. Quý vị có thể phải thực hiện theo thông báo đúng trong thời hạn
để duy trì bảo hiểm sức khỏe hoặc được trợ giúp thêm về chi phí. Quý vị có
quyền được biết thông tin này và được trợ giúp bằng ngôn ngữ của mình
miễn phí. Xin gọi số 800-722-1471 (TTY: 800-842-5357).