Medical Policy


Subject: Preconception or Prenatal Genetic Testing of a Parent or Prospective Parent
Document #: GENE.00012 Publish Date:    06/06/2018
Status: Revised Last Review Date:    05/03/2018

Description/Scope

This document addresses preconception or prenatal genetic testing on a parent or prospective parent to determine carrier status of an autosomal recessive disorder, an x-linked disorder, or a disorder with variable penetrance.  The testing is typically done prior to pregnancy to guide reproductive decisions.

Notes:

Other related documents include:

Position Statement

Note: Genetic counseling should be a component of a decision to perform genetic testing

Medically Necessary:

  1. Preconception or prenatal genetic screening of a parent or prospective parent to determine carrier status of inherited disorders is considered medically necessary when both sets (A and B) of the following criteria are met:
    1. Criteria based on family history
      Genetic screening of the parent or prospective parent is considered medically necessary when one of the following criteria is met.
      1. An affected child is identified with either an autosomal recessive disorder, an x-linked disorder, or an inherited disorder with variable penetrance and genetic testing is performed to determine the pattern of inheritance and to guide subsequent reproductive decisions; or
      2. One or both parents or prospective parent(s) have another first or a second degree relative who is affected, or the first degree relative has an affected child, with either an autosomal recessive disorder, an x-linked disorder, or an inherited disorder with variable penetrance and genetic testing is performed to determine the pattern of inheritance and to guide subsequent reproductive decisions; or
      3. The parent or prospective parent is at high risk for a genetic disorder with a late onset presentation, and genetic testing is performed to determine carrier status and to guide subsequent reproductive decisions; or
      4. The parent or prospective parent is a member of an ethnic group with a high risk of a specific genetic disorder with an autosomal recessive pattern of inheritance and genetic testing is performed to determine carrier status and to guide subsequent reproductive decisions, including but not limited to Tay-Sach’s disease, Canavan disease, familial dysautonomia, mucolipidosis IV, Niemann Pick Disease Type A, Fanconi anemia group C, Bloom syndrome or Gaucher disease.
    2. Criteria for Specific Genetic Test
      In the parent or prospective parent who meets one of the applicable criteria above, specific genetic testing is considered medically necessary when all of the following criteria are met:
      1. A specific mutation, or set of mutations, has been established in the scientific literature to be reliably associated with the disease; and
      2. The genetic disorder is associated with a potentially severe disability or has a lethal natural history; and
      3. A biochemical or other test is identified but the results are indeterminate, or the genetic disorder cannot be identified through biochemical or other testing; and
      4. Genetic counseling, which encompasses all of the following components, has been performed:
        1. Interpretation of family and medical histories to assess the probability of disease occurrence or recurrence; and
        2. Education about inheritance, genetic testing, disease management, prevention and resources; and
        3. Counseling to promote informed choices and adaptation to the risk or presence of a genetic condition; and
        4. Counseling for the psychological aspects of genetic testing.
  2. Routine preconception or prenatal genetic screening of a parent or prospective parent to determine carrier status of cystic fibrosis, using a standard panel usually consisting of 23 or more of the common gene mutations, is considered medically necessary
  3. Preconception or prenatal genetic screening of a parent or prospective parent to determine carrier status of spinal muscular atrophy is considered medically necessary.

Not Medically Necessary:

Routine preconception or prenatal genetic screening of a parent or prospective parent to determine carrier status of cystic fibrosis, using complete DNA sequencing of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is considered not medically necessary.

Routine preconception or prenatal genetic screening of a parent or prospective parent to determine carrier status of cystic fibrosis, using gene analysis of known CFTR familial variants, is considered not medically necessary.

Routine preconception or prenatal genetic screening of a parent or prospective parent to determine carrier status of cystic fibrosis, using gene analysis of CFTR duplication/deletion variants, is considered not medically necessary.

Investigational and Not Medically Necessary:

Preconception or prenatal genetic testing of a parent or prospective parent for inherited medical disorders including but not limited to amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease), that do not meet the above criteria is considered investigational and not medically necessary.  

Preconception or prenatal genetic testing of a parent or prospective parent using panels of genes (with or without next generation sequencing), including but not limited to whole genome and whole exome sequencing, is considered investigational and not medically necessary unless all components of the panel have been determined to be medically necessary based on the criteria above.  However, individual components of a panel may be considered medically necessary when criteria above are met.

Rationale

Carrier testing for inherited genetic conditions is a key component of preconception and prenatal care.  Carrier testing is conducted to identify an individual or a couple at risk (parent or prospective parent) for passing on genetic conditions to their offspring.  Carriers are asymptomatic individuals who are typically not at risk for developing the disease, but possess the potential to pass the gene mutation to their offspring.  Carrier testing is frequently performed on the parent or prospective parent before conception or during a pregnancy.

Carrier screening may be conducted for conditions that are found in the general population (panethnic), for diseases that are more common in a particular population, or based on family history.  Panethnic screening (population screening) for carrier status is done for single-gene disorders that are common in the population.

Preconception or prenatal genetic testing of a parent or prospective parent is a common practice to determine carrier status.  For example, the American College of Obstetrics and Gynecology (ACOG) and the American College of Medical Genetics (ACMG) recommend carrier screening for Tay-Sach’s disease, Canavan disease, mucolipidosis IV, Niemann Pick Disease Type A, Fanconi anemia group C, Bloom syndrome, Gaucher’s disease and familial dysautonomia among individuals of Ashkenazi Jewish descent (ACOG, 2009; Gross, 2008).  With regards to Fragile X syndrome, the ACMG provides guidance on prenatal and preconception testing and ACOG has published a Committee Opinion for carrier screening (Sherman, 2005; ACOG, 2009; ACOG, 2010; ACOG, 2017[b]).

There has also been a growing interest in the use of genetic testing for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.  ALS is a progressive neurodegenerative disorder that affects nerve cells in the spinal cord and brain which eventually results in paralysis and death.

Cystic Fibrosis
Cystic fibrosis (CF) is a hereditary disease which affects many organs throughout the body and most of the exocrine glands.  As a result of the abnormal production of secretions, CF leads to organ and tissue damage, especially in the airways, liver, pancreas, intestines, sweat glands, and, in males, the vas deferens.  While several organs and tissues are affected by CF, pulmonary disease remains the predominant cause of morbidity and mortality in individuals with CF.  It has been estimated approximately 1 in every 31 Americans is an asymptomatic carrier of the defective CF gene. 

CF results when an individual inherits a gene mutation in both alleles of the CF transmembrane conductance regulator (CFTR) gene, located on chromosome 7q31.  The CFTR gene produces a protein that functions as a chloride channel and regulates both bicarbonate and chloride transport.  The CFTR gene product is also involved in other transport pathways.  More than 1900 different mutations in the CF gene have been identified.  The prevalence of carrier frequencies and mutation types varies among populations.  Non-Hispanic whites of Northern European descent have a carrier rate of 1 in 25 with the ΔF508 mutation being the most common.  It has been estimated that amongst individuals of Ashkenazi Jewish descent, CFTR mutation carrier frequency is 1 in 24.  When considered all together, the most common mutations in this population (W1282X, ΔF508, G542X, 3849+10kb C>T, and N1303K) account for at least 94% of the CF cases.

The clinical severity of an individual’s symptoms is largely determined by the specific mutations that an individual carries.  Any individual who screens positive for CF should receive genetic counseling.  Negative screening results reduce but do not totally eliminate the possibility that the individual is a CF carrier.  A negative screening test indicates only that the individual does not carry any of the CF mutations tested for during the screening. 

Due to the high prevalence of carriers of CF, ACOG and ACMG recommend that DNA screening for CF be made available to all individuals seeking preconception or prenatal care regardless of personal or family history for the disease or carrier status (ACOG, 2017[a], 2017[b]). The National Society of Genetic Counselors (NSGC) recommends that carrier testing for CF be provided to women of reproductive age, regardless of ancestry.  The NSGC also recommends that prior to conception “CF carrier testing should also be offered to any individual with a family history of CF and to partners of mutation carriers and people with CF” (Langfelder-Schwind, 2014).

Because so many different mutations in the CF gene have been identified, it is impractical to test for every known mutation.  In 2001, the ACMG Accreditation of Genetic Services Committee compiled a standard screening panel of 25 CF mutations to screen for CF in the U.S. population (Grody et al, 2001).  This 25-mutation panel incorporated all CF-causing mutations with an allele frequency of greater than or equal to 0.1 % in the general U.S. population.  The panel also included mutation subsets shown to be sufficiently predominant in certain ethnic groups, such as African Americans and Ashkenazi Jews.  The ACMG recommended that this standard panel of mutations be used to provide the greatest pan-ethnic detectability that can practically be performed.  In the 2004 guidelines on CF population carrier screening, the ACMG recommended using a panel that contains, at a minimum, 23 of the most common CF mutations (Watson, 2004).

According to NSGC, carrier testing panels should include the mutations recommended by ACOG and ACMG.  For individuals of non-Northern European descent, panethnic panels that include additional mutations more commonly identified in minority populations are appropriate to consider.  NSGC also recommends that general population screening practices focus on “identifying carriers of established disease-causing CFTR mutations” (Langfelder-Schwind, 2014). 

In a recent Consensus Opinion, ACOG stipulated that:

Complete analysis of the CFTR gene by DNA sequencing is not appropriate for routine carrier screening.  This type of testing generally is reserved for patients with cystic fibrosis, patients with negative carrier screening result but a family history of cystic fibrosis (especially if family test results are not available), 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 it will add value to the standard screening that was performed previously (ACOG, 2017[b]).

Spinal Muscular Atrophy
Spinal muscular atrophy (SMA) is a disease characterized by muscle atrophy and weakness caused by the progressive degeneration and loss of the brain stem nuclei and the anterior horn cells in the spinal cord (i.e., lower motor neurons).  The onset of muscle weakness ranges from before birth to adolescence or young adulthood.  The weakness is symmetrical and progresses from proximal to distal.  Growth failure and poor weight gain, restrictive lung disease, scoliosis, joint contractures, and sleep difficulties are common complications (Prior, 2016).  The age of the onset of symptoms roughly correlates with the extent to which motor function is affected:  The earlier the age of onset, the more profound the impact on motor function.  Children who are symptomatic at birth or in infancy typically have the lowest level of function. 

SMA is caused by a mutation in the survival motor neuron gene (SMN1).  Due to the severity of the disease and the relatively high carrier frequency, there has been interest in carrier screening for SMA in the general prenatal population.  Because the genetics of SMA are complex and due to “limitations in the molecular diagnostic assays available, precise prediction of the phenotype in affected fetuses may not be possible” (ACOG, 2017[b]).

ACOG Committee Opinion No. 690 Carrier Screening in the Age of Genomic Medicine and No. 691 Carrier Screening for Genetic Conditions indicates that all individuals who are considering pregnancy or are already pregnant, regardless of screening strategy and ethnicity, should be offered carrier screening for SMA (ACOG 2017[a], ACOG 2017[b]).

The ACMG position statement on Carrier Screening for Spinal Muscular Atrophy recommends panethnic screening for SMA (Prior, 2008).

Expanded Carrier Screening and Panels
Advances in genetic testing technologies have led to the development and use of large-scale DNA sequencing, including but not limited to expanded carrier panels.

Generally, carrier screening guidelines have focused on the assessment of individual conditions and ancestry.  However, the effectiveness of this approach can be impacted by limited or inaccurate knowledge of ancestry and an increasingly multiethnic society.  Approaches to screening have also been influenced by the recognition that while some genetic conditions occur more frequently in certain populations, genetic disorders are not limited to specific ethnic groups (Edwards, 2015). 

According to the ACMG:

The completion of the full human genome sequence, followed by dramatic improvement in the speed and cost of DNA sequencing and microarray hybridization analysis, has enabled the ascertainment of an unprecedented quantity of disease-specific genetic variants in a time frame suited to prenatal/preconception screening and diagnosis.  Now it is possible, using new technologies, to screen for mutations in many genes for approximately the same cost as previously required to detect mutations in a single gene or a relatively small number of population-specific mutations in several genes.  Commercial laboratories have begun to offer such expanded carrier screening panels to physicians and the public, but there has been no professional guidance on which disease genes and mutations to include (Grody, 2013).

Previously, testing for a specific genetically linked condition typically began by identifying the most commonly associated genetic variants first and, if there was a high degree of suspicion, progressed in a step-wise fashion to identify variants that are less common.  However, recent advances in next-generation sequencing (also known as massively parallel sequencing) technologies permit the sequencing of millions of fragments of DNA in a relatively short period of time and enable the efficient screening of vast numbers of conditions simultaneously.  As a result of the advances made in the area of next generation sequencing (NGS), researchers have been exploring the use of expanded carrier screening (ECS) tests that utilize next generation sequencing technologies to access carrier status for a host of genetic conditions simultaneously.  ECS has been described as “the practice of screening all individuals for dozens to hundreds of diseases, some with lower frequencies or severity grades, typically without tailoring to a person’s reported ethnicity” (Edwards, 2015; Lazarin, 2015). 

Next generation sequencing (NGS) provides information pertaining to conditions beyond those that are currently recommended in screening guidelines.  At present, professional practice guidelines recommend offering carrier screening for individual conditions based on the severity of the condition, race or ethnicity, prevalence, carrier frequency, detection rates, and residual risk. 

The 2013 ACMG Position Statement on Prenatal/Preconception Expanded Carrier Screening indicates that the proper selection of appropriate disease-causing targets for general population-based carrier screening (that is, absence of a family history of the disorder) should be developed using clear criteria, rather than simply including as many disorders as possible.  In order for a particular disorder to be included in carrier screening, the following criteria should be fulfilled:

  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.
    • 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 the offspring of the individual undergoing carrier screening once the offspring reaches adult life) are included in screening panels, patients must provide consent to screening for these conditions, especially when there may be implications for the health of the individual being screened or other family members.
    • 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.
    • Laboratories should specify in their marketing literature and test results how residual risk was calculated using panethnic population data or a specific race/ethnic group.
    • 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 overinterpreted.
  4. There must be validated clinical association between the mutation(s) detected and the severity of the disorder.
    • Patient and provider materials must include specific citations that support inclusion of the mutations for which screening is being performed.
  5. Compliance with the American College of Medical Genetics and Genomics Standards and Guidelines for Clinical Genetics Laboratories, including quality control and proficiency testing.
    • 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 (Grody, 2013).

The joint statement issued by ACMG, ACOG, the Society for Maternal-Fetal Medicine, NSGC, and the Perinatal Quality Foundation stops short of endorsing the use of ECS tests and provides a general overview of the expanded screening paradigm.  This collaborative statement points out several limitations of ECS.  In the context of ECS, all individuals, regardless of ethnicity or race, are offered screening for the same set of conditions and ECSPs, (also known as expanded carrier screening panels, expanded panels and expanded carrier panels [ECPs]) which may include more than 100 genetic conditions, most of which are rare.  Although the majority of conditions on current expanded panels are autosomal-recessive, it is possible that some may be X-linked or autosomal-dominant single-gene conditions.  The authors also maintain that while expanded screening panels include most of the conditions recommended in current guidelines, the molecular methods used in ECS are not as accurate as methods recommended in current guidelines for the hemoglobinopathies and Tay-Sachs disease (Edwards, 2015).

While ECS delivers more comprehensive screening, this method presents challenges in clinical management.  Traditional methods of carrier screening generally have focused on conditions that have a significant impact on the quality of life as a result of physical or cognitive disabilities, require lifelong medical therapies and have a fetal, neonatal or early childhood onset as well as a well-defined phenotype.  In contrast, the ECPs often include conditions for which carrier screening of the general population is not recommended by current practice guidelines (for example factor V Leiden and hemochromatosis).  While some genetic variants on expanded panels have a relatively consistent phenotype, others are less clearly defined.  ECPs may also include other conditions that have significant variation in their presentation and variable age of onset.  Additionally, expanded panels may include rare conditions for which the precise carrier frequency of condition-causing variants may be unknown (Edwards, 2015; Grody, 2001; Monaghan, 2013; USPSTF, 2006). 

The joint statement includes the following recommendations regarding the use of ECPs:

  1. The condition being screened for should be a health problem that encompasses one or more of the following:
    1. Cognitive disability.
    2. Need for surgical or medical intervention.
    3. Effect on quality of life.
    4. Conditions for which a prenatal diagnosis may result in:
      1. Prenatal intervention to improve perinatal outcome and immediate care of the neonate.
      2. Delivery management to optimize newborn and infant outcomes such as immediate, specialized neonatal care.
      3. Prenatal education of parents regarding special needs care after birth; this often may be accomplished most effectively before birth (Edwards, 2015).

Finally, the authors point out that:

Expanded carrier screening panels may include rare conditions; for such disorders, the precise carrier frequency as well as the proportion of condition-causing variants that can be detected may be unknown.  Therefore, calculation of residual risk after a negative screening test may not be possible for all conditions (Edwards, 2015).

Despite the fact that ECS tests are increasingly being utilized, there is currently a lack of guidance from specialty associations and societies identifying the population that is appropriate to undergo screening using these tests or which genes should be included in the panels.  While many of the targeted carrier screening tests have reported high analytic validity, the analytic validity of ECSPs is either unknown or cannot be sufficiently assessed due to weakness in assay validation.  It is also difficult to determine the clinical validity of carrier screening because by definition, carriers have no symptoms of the diseases being tested, and thus the association of the carrier state is impossible to define.  For this reason, it is impossible to determine whether a negative test is a true-negative or a false-negative due to the inability to define the carrier state in clinical terms.  Lastly, with regards to clinical utility, there is a lack of evidence demonstrating that expanded carrier testing in individuals who are asymptomatic but at risk for having an offspring with a genetic disease, results in improved clinical outcomes (for example, reduces the number of births with an inherited disorder) or impacts management (for example, changes family planning decisions).

Clinical laboratories may develop and validate screening tests or panels in-house (“home-brew”) and market them as a laboratory service; such tests or panels are subject to the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA).

There are currently several commercially available laboratory developed tests for carrier screening.  These tests range from tests designed to test for individual diseases, to panels based on ethnicity as recommended in specialty association or society guidelines, to large expanded panels that test for many diseases beyond those recommended in practice guidelines.  These panels include but are not necessarily limited to the following:

Whole Genome Sequencing

Whole genome sequencing (WGS), also known as full genome sequencing (FGS), complete genome sequencing, or entire genome sequencing, is a laboratory procedure which seeks to determine an individual's entire DNA sequence, specifying the order of every base pair within the genome at a single time.  WGS allows researchers to study the 98% of the genome that does not generally contain protein-coding genes.  In the clinical setting, this process frequently involves obtaining a DNA sample from the individual (typically from blood, saliva or bone marrow) and sequencing an individual's entire chromosomal and mitochondrial DNA.  Because of the large volume of genomic data involved in this process, the genomic information is processed by and stored on microprocessors and computers.

The clinical role of WGS has yet to be established.  Research is still being done to determine if WGS can be used to accurately identify the presence of a disease, predict the development of a particular disease in asymptomatic individuals as well as how an individual might respond to pharmacological therapy.  It has been theorized that WGS might eventually improve clinical outcomes by preventing the development of disease.

Whole Exome Sequencing

While similar to whole genome sequencing, whole-exome sequencing (WES) reads only the parts of the human genome that encode proteins, leaving the other regions of the genome unread (Choi, 2009).  Since most of the errors that occur in DNA sequences that then lead to genetic disorders are located in the exons, sequencing of the exome is being explored as a more efficient method of analyzing an individual's DNA to discover the genetic cause of diseases or disabilities.  It has been theorized that sequencing of the human exome can be used to identify genetic variants in individuals in order to diagnose diseases without the high cost associated with WGS.

A potential major indication for use is molecular diagnosis of individuals with a phenotype that is suspicious for a genetic disorder or for individuals with known genetic disorders that have a large degree of genetic heterogeneity involving substantial gene complexity.  Such individuals may be left without a clinical diagnosis of their disorder, despite a lengthy diagnostic work-up involving a variety of traditional molecular and other types of conventional diagnostic tests.  For some of these individuals, WES, after initial conventional testing has failed to make the diagnosis, may return a likely pathogenic variant.

While some of the potential advantages of WES include the fact that it can be carried out more quickly than traditional genetic testing and it may be less expensive than some other tests (for example, WGS), it is not without limitations.  WES typically covers only 85–95% of the exome and has no, or limited coverage of other areas of the genome.  Areas of concern with this technology include: (1) gaps in the identification of exons prior to sequencing; (2) the need to narrow the large initial number of variants to manageable numbers without losing the likely candidate mutation; (3) difficulty identifying the potential causative variant when large numbers of variants of unknown significance are generated for each individual.  It is more difficult to detect chromosomal changes, duplications, large deletions, rearrangements, epigenetic changes or nucleotide repeats from WES data compared with other genomic technologies (ACMG, 2012; National Cancer Institute, 2012; Teer, 2010[a]; Teer, 2010[b]).

At this time, there are limitations to WES that prohibit its use in routine clinical care.  The limited experience with WES on a population level leads to gaps in understanding and interpreting ancillary information and variants of uncertain significance.  As a result, the risk/benefit ratio of WES testing is poorly defined.  Because the peer-reviewed literature on WES for clinical purposes consists primarily of case reports and small case series, the clinical applications of WES have yet to be established (Bilguvar, 2010; Choi, 2009; Clayton-Smith, 2011, Saitsu, 2011; Vissers, 2011).

WES and WGS present ethical questions about informing individuals about incidental findings that have clinical significance.  Ongoing discussions continue to explore whether or not, and how to inform individuals about medically relevant mutations in genes unrelated to the diagnostic question (that is, mutations of unknown significance, non-paternity and sex chromosome abnormalities).  This type of information may not only affect the individual being tested, but may also implicate family members.

In 2013, the AMCG charged a Working Group with evaluating the need for principles that would govern recommendations for analyzing and reporting incidental findings from genome and exome sequencing in the clinical context.  However, the Work Group recommendations do not address preconception sequencing, prenatal sequencing, newborn sequencing, or sequencing of healthy children and adults (Green, 2013).

The ACMG (2012) published a position statement addressing points to consider in the clinical application of genomic sequencing.  The policy statement:

Was developed primarily as an educational resource for clinical and laboratory geneticists to help them provide quality clinical and laboratory genetic services.  Adherence to these Points to Consider is voluntary and, in determining the relevance of and weight to be given to any specific point, the clinical and laboratory geneticist should apply his or her own professional judgment to the specific circumstances presented by the individual patient or specimen.

The document contains indications for whole genome and WES as both screening and diagnostic tools.  The ACMG indicates that diagnostic testing using whole genome or WES is indicated for the following phenotypically affected individuals:

Specifically regarding WES and WGS in the prenatal setting, the ACMG states the following:

Prenatal diagnosis by genomic (i.e., next-generation whole-exome or whole-genome) sequencing has significant limitations.  The current technology does not support short turnaround times, which are often expected in the prenatal setting.  There are high rates of false positives, false negatives, and variants of unknown clinical significance.  These can be expected to be significantly higher than seen when array CGH is used in prenatal diagnosis (2012).

Background/Overview

Preconception or prenatal genetic testing of a parent or prospective parent is an accepted practice to determine carrier status (identify couples at risk for passing on specific genetic conditions to their children).  There are a growing number of diseases for which a genetic basis has been identified.

Cystic Fibrosis
CF is a life-limiting autosomal recessive disease affecting the respiratory tract, pancreas, liver, intestines, sweat glands, and, in males, the vas deferens.  CF is a common genetic disorder in select populations, including, but not limited to non-Hispanic whites of Northern European descent.  Carrier screening is offered to couples planning pregnancy or in early pregnancy to identify those at risk of conceiving a child with CF.

Spinal Muscular Atrophy
SMA is a genetic disease that affects the part of the nervous system that controls voluntary muscle movement.  Individuals with SMA lose the ability to walk, eat, or breathe.  SMA is brought about by a mutation in the survival motor neuron gene 1.  SMA is one of the most common autosomal recessive conditions of childhood.

Genetic Counseling
According to the NSGC, genetic counseling is the process of assisting individuals to understand and adapt to the medical, psychological and familial ramifications of a genetic disease.  This process typically includes the guidance of a specially trained professional who:

  1. Integrates the interpretation of family and medical histories to assess the probability of disease occurrence or recurrence; and
  2. Provides education about inheritance, genetic testing, disease management, prevention and resources; and
  3. Provides counseling to promote informed choices and adaptation to the risk or presence of a genetic condition; and
  4. Provides counseling for the psychological aspects of genetic testing (NSGC, 2006).
Definitions

Amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease): A progressive neurodegenerative disorder that affects nerve cells in the spinal cord and brain which eventually results in paralysis and death.

Analytical validity: The accuracy with which a test identifies the presence or absence of a particular gene or genetic change (mutation).

Ashkenazi Jewish: A term for people of eastern European Jewish heritage.

Carrier: An individual who is asymptomatic (or has only mild symptoms) of a disorder but has the potential to pass on the gene for that disorder to his or her offspring.

Clinical validity: The accuracy with which a test identifies or predicts an individual's clinical status.

Cystic fibrosis (CF): An inherited disease that affects the mucus and sweat glands of the body; thick mucus is formed in the breathing passages of the lungs that predisposes the person to chronic lung infections.

Ethnicity: Coming from a large group that shares racial, national, language or cultural characteristics.

Expanded panels: Genetic testing panels that employ next generation sequencing to screen for mutations in numerous genes, as opposed to gene-by-gene screening.

First-degree relative: Any relative who is a parent, sibling, or offspring to another.

Genetic molecular testing: A type of test that is used to determine the presence or absence of a specific gene or set of genes to help diagnose a disease, screen for specific health conditions, and for other purposes.

Genome: An organism’s entire set of DNA.

Mutation: A change in DNA sequence.

Next-generation sequencing: Any of the technologies that allow rapid sequencing of large numbers of segments of DNA, up to and including entire genomes.

Panethnic screening: A screening approach that is done for single-gene disorders based on ethnicity, race, or both.

Second-degree relative: Any relative who is a grandparent, grandchild, uncle, aunt, niece, nephew, or half-sibling to another.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Medically Necessary for preconception/prenatal testing:

CPT

 

81200

ASPA (aspartoacylase) (eg, Canavan disease) gene analysis, common variants (eg, E285A, Y231X)

81209

BLM (Bloom syndrome, RecQ helicase-like) (eg, Bloom syndrome) gene analysis, 2281del6ins7 variant

81220

CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; common variants (eg, ACMG/ACOG guidelines)

81224

CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; intron 8 poly-T analysis (eg, male infertility)

81241

F5 (coagulation Factor V) (eg, hereditary hypercoagulability) gene analysis, Leiden variant

81242

FANCC (Fanconi anemia, complementation group C) (eg, Fanconi anemia, type C) gene analysis, common variant (eg, IVS4+4A>T)

81251

GBA (glucosidase, beta, acid) (eg, Gaucher disease) gene analysis, common variants (eg, N370S, 84GG, L444P, IVS2+1G>A)

81252

GJB2 (gap junction protein, beta 2, 26kDa, connexin 26) (eg, nonsyndromic hearing loss) gene analysis; full gene sequence

81253

GJB2 (gap junction protein, beta 2, 26kDa, connexin 26) (eg, nonsyndromic hearing loss) gene analysis; known familial variants

81254

GJB2 (gap junction protein, beta 6, 30kDa, connexin 30) (eg, nonsyndromic hearing loss) gene analysis, common variants (eg, 309kb [del(GJB6-D13S1830)] and 232kb [del(GJB6-D13S1854)])

81255

HEXA (hexosaminidase A [alpha polypeptide]) (eg, Tay-Sachs disease) gene analysis, common variants (eg, 1278insTATC, 1421+1G>C, G269S)

81256

HFE (hemochromatosis) (eg, hereditary hemochromatosis) gene analysis, common variants (eg, C282Y, H63D)

81257

HBA1/HBA2 (alpha globin 1 and alpha globin 2) (eg, alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis; common deletions or variant (eg, Southeast Asian, Thai, Filipino, Mediterranean, alpha3.7, alpha4.2, alpha20.5, and Constant Spring)

81258

HBA1/HBA2 (alpha globin 1 and alpha globin 2) (eg, alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis; known familial variant

81259

HBA1/HBA2 (alpha globin 1 and alpha globin 2) (eg, alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis; full gene sequence

81260

IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) (eg, familial dysautonomia) gene analysis, common variants (eg, 2507+6T>C, R696P)

81269

HBA1/HBA2 (alpha globin 1 and alpha globin 2) (eg, alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis; duplication/deletion variants

81290

MCOLN1 (mucolipin 1) (eg, Mucolipidosis, type IV) gene analysis, common variants (eg, IVS3-2A>G, del6.4kb)

81330

SMPD1(sphingomyelin phosphodiesterase 1, acid lysosomal) (eg, Niemann-Pick disease, Type A) gene analysis, common variants (eg, R496L, L302P, fsP330)

81361

HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); common variant(s) (eg, HbS, HbC, HbE)

81362

HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); known familial variant(s)

81363

HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); duplication/deletion variant(s)

81364

HBB (hemoglobin, subunit beta) (eg, sickle cell anemia, beta thalassemia, hemoglobinopathy); full gene sequence

81412

Ashkenazi Jewish associated disorders (eg, Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia group C, Gaucher disease, Tay-Sachs disease), genomic sequence analysis panel, must include sequencing of at least 9 genes, including ASPA, BLM, CFTR, FANCC, GBA, HEXA, IKBKAP, MCOLN1, and SMPD1

 

 

HCPCS

 

S3841

Genetic testing for retinoblastoma

S3842

Genetic testing for von Hippel-Lindau disease

S3844

DNA analysis of the connexin 26 gene (GJB2) for susceptibility to congenital, profound deafness

S3845

Genetic testing for alpha-thalassemia

S3846

Genetic testing for hemoglobin E beta-thalassemia

S3849

Genetic testing for Niemann-Pick diseases

S3853

Genetic testing for myotonic muscular dystrophy

 

 

ICD-10 Diagnosis

 

Z31.430

Encounter of female for testing for genetic disease carrier status for procreative management

Z31.440

Encounter of male for testing for genetic disease carrier status for procreative management

Z36.0

Encounter for antenatal screening for chromosomal anomalies

Z36.8A

Encounter for antenatal screening for other genetic defects

Z84.81

Family history of carrier of genetic disease

When services are also Medically Necessary for preconception/prenatal testing:

CPT

 

81401

Molecular pathology procedure, Level 2 (eg, 2-10 SNPs, 1 methylated variant, or 1 somatic variant [typically using nonsequencing target variant analysis], or detection of a dynamic mutation disorder/triplet repeat) [when specified as the following]:

  • SMN1/SMN2 (survival of motor neuron 1, telomeric/survival of motor neuron 2 centromeric) (eg, spinal muscular atrophy), dosage analysis (eg, carrier testing)

ICD-10 Diagnosis

 

Z31.430

Encounter of female for testing for genetic disease carrier status for procreative management

Z31.440

Encounter of male for testing for genetic disease carrier status for procreative management

When services are Not Medically Necessary for preconception/prenatal testing:

CPT

 

81221

CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; known familial variants

81222

CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; duplication/deletion variants

81223

CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; full gene sequence

 

 

ICD-10 Diagnosis

 

Z31.430

Encounter of female for testing for genetic disease carrier status for procreative management

Z31.440

Encounter of male for testing for genetic disease carrier status for procreative management

When services are Investigational and Not Medically Necessary for preconception/prenatal testing:

CPT

 

81403

Molecular pathology procedure, Level 4 (eg, analysis of single exon by DNA sequence analysis, analysis of >10 amplicons using multiplex PCR in 2 or more independent reactions, mutation scanning or duplication/deletion variants of 2-5 exons) [when specified as the following]:

  • ANG (angiogenin, ribonuclease, RNase A family, 5) (eg, amyotrophic lateral sclerosis), full gene sequence

81404

Molecular pathology procedure, Level 5 (eg, analysis of 2-5 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 6-10 exons, or characterization of a dynamic mutation disorder/triplet repeat by Southern blot analysis) [when specified as the following]:

  • SOD1 (superoxide dismutase 1, soluble) (eg, amyotrophic lateral sclerosis), full gene sequence

81405

Molecular pathology procedure, Level 6 (eg, analysis of 6-10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 11-25 exons, regionally targeted cytogenomic array analysis) [when specified as the following]:

  • TARDBP (TAR DNA binding protein) (eg, amyotrophic lateral sclerosis), full gene sequence

81406

Molecular pathology procedure, Level 7 (eg, analysis of 11-25 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 26-50 exons, cytogenomic array analysis for neoplasia) [when specified as the following]:

  • FUS (fused in sarcoma) (eg, amyotrophic lateral sclerosis), full gene sequence;
  • OPTN (optineurin) (eg, amyotrophic lateral sclerosis), full gene sequence

HCPCS

 

S3800

Genetic testing for amyotrophic lateral sclerosis (ALS)

 

 

ICD-10 Diagnosis

 

G12.21

Amyotrophic lateral sclerosis

When services are also Investigational and Not Medically Necessary for preconception/prenatal testing:

CPT

 

81479

Unlisted molecular pathology procedure [when specified as preconception or prenatal testing using panels of genes (with or without next generation sequencing)]

81415

Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis

81416

Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator exome (eg, parents, siblings)

81417

Exome (eg, unexplained constitutional or heritable disorder or syndrome); re-evaluation of previously obtained exome sequence (eg, updated knowledge or unrelated condition/syndrome)

81425

Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis

81426

Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator exome (eg, parents, siblings)

81427

Genome (eg, unexplained constitutional or heritable disorder or syndrome); re-evaluation of previously obtained genome sequence (eg, updated knowledge or unrelated condition/syndrome)

0012U

Germline disorders, gene rearrangement detection by whole genome next-generation sequencing, DNA, whole blood, report of specific gene rearrangement(s)
MatePair Targeted Rearrangements, Congenital, Mayo Clinic

 

 

ICD-10 Diagnosis

 

 

All diagnoses

References

Peer Reviewed Publications:

  1. Bilguvar K, Ozturk AK, Louvi A, et al. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature. 2010; 467(7312):207-210.
  2. Choi M, Scholl UI, Ji W, et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci U S A. 2009; 106(45):19096-19101.
  3. Clayton-Smith J, O'Sullivan J, Daly S, et al. Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome. Am J Hum Genet. 2011; 89(5):675-681.
  4. Lazarin GA, Haque IS. Expanded carrier screening: A review of early implementation and literature. Semin Perinatol. 2016; 40(1):29-34.
  5. Mailman MD, Heinz JW, Papp AC, et al. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002; 4(1):20-26.
  6. Prior TW, Finanger E. Spinal muscular Atrophy. 2000 [Updated 2016]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1352/. Accessed on March 1, 2018.
  7. Prior TW, Snyder PJ, Rink BD, et al. Newborn and carrier screening for spinal muscular atrophy. Am J Med Genet A. 2010; 152A (7):1608-1616.
  8. Rose NC, Wick M. Current recommendations: Screening for Mendelian disorders. Semin Perinatol. 2016; 40(1):23-8.
  9. Saitsu H, Osaka H, Sasaki M, et al. Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. Am J Hum Genet. 2011; 89(5):644-651.
  10. Teer JK, Bonnycastle LL, Chines PS, et al. Systematic comparison of three genomic enrichment methods for massively parallel DNA sequencing. Genome Res. 2010(a) 20(10):1420-1431.
  11. Teer JK, Mullikin JC. Exome sequencing: the sweet spot before whole genomes. Hum Mol Genet. 2010(b) 19(R2):R145-151.
  12. Vissers LE, Fano V, Martinelli D, et al. Whole-exome sequencing detects somatic mutations of IDH1 in metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA). Am J Med Genet A. 2011; 155A (11):2609-2616.
  13. Weinstein LB. Selected genetic disorders affecting Ashkenazi Jewish families. Fam Community Health. 2007 30(1):50-62.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. ACMG Board of Directors. Points to consider in the clinical application of genomic sequencing. Genet Med. 2012; 14(8):759-761.
  2. American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent. Obstet Gynecol. 2009; 114(4):950-953. Reaffirmed 2014.
  3. American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee Opinion No. 469: Carrier screening for fragile X syndrome. Obstet Gynecol. 2010; 116(4):1008-1010.
  4. American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee Opinion No. 486: Update on carrier screening for cystic fibrosis. Obstet Gynecol. 2011; 117(4):1028-1031. Reaffirmed 2014.
  5. American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee Opinion No. 690: Carrier screening in the age of genomic medicine. Obstet Gynecol. 2017(a); 129(3):e35-e40.
  6. American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee Opinion No. 691. Carrier screening for genetic conditions. Obstet Gynecol. 2017(b); 129(3):e41-e45.
  7. 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. 2015; 125(3):653-662.
  8. Green RC, Berg JS, Grody WW, et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013; 15(7):565-574.
  9. Gross SJ, Pletcher BA, Monaghan KG; et al. Carrier screening in individuals of Ashkenazi Jewish descent. Genet Med. 2008; 10(1):54-56.
  10. Grody WW, Cutting GR, Klinger KW, et al. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet Med. 2001; 3(2):149-154.
  11. Grody WW, Griffin JH, Taylor AK, et al. American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genet Med. 2001; 3(2):139-148.
  12. Grody WW, Thompson BH, Gregg AR, et al. ACMG position statement on prenatal/preconception expanded carrier screening. Genet Med. 2013; 15(6):482-483.
  13. Langfelder-Schwind E, Karczeski B, Strecker MN, et al. Molecular testing for cystic fibrosis carrier status practice guidelines: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2014; 23(1):5-15.
  14. Monaghan KG, Lyon E, Spector EB; American College of Medical Genetics and Genomics. ACMG Standards and Guidelines for fragile X testing: a revision to the disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics and Genomics. Genet Med. 2013; 15(7):575-586.
  15. National Society of Genetic Counselors. Genetic Counselor Scope of Practice. Available at: https://www.nsgc.org/p/cm/ld/fid=18#scope. Accessed on April 12, 2018.
  16. National Society of Genetic Counselors' Definition Task Force, Resta R, Biesecker BB, et al. A new definition of Genetic Counseling: National Society of Genetic Counselors' Task Force report. J Genet Couns. 2006; 5(2):77-83.
  17. Prior TW; Professional Practice and Guidelines Committee. Carrier screening for spinal muscular atrophy. Genet Med. 2008; 10(11):840-842.
  18. Sherman S, Pletcher BA, Driscoll DA. Fragile X syndrome: diagnostic and carrier testing. Genet Med. 2005; 7(8):584-587.
  19. U.S. Preventive Services Task Force. Screening for hemochromatosis: recommendation statement. Ann Intern Med. 2006; 145(3):204-208.
  20. 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. 2004; 6(5):3873-91.
Websites for Additional Information
  1. American Board of Genetic Counselors. About genetic counseling. Available at: https://www.abgc.net/about-genetic-counseling/. Accessed on April 12, 2018.
  2. American College of Obstetricians and Gynecologists. Frequently asked questions. FAQ179. Pregnancy. Preconception Carrier Screening (2017). Available at: https://www.acog.org/~/media/For%20Patients/faq179.pdf. Accessed on April 12, 2018.
  3. National Library of Medicine (NLM). Genetics Home Reference. What are the types of genetic tests? Published February 27, 2018. Available at: https://ghr.nlm.nih.gov/primer/testing/uses. Accessed on April 12, 2018.
Index

Bloom Syndrome
Canavan Disease
Counsyl Family Prep Screen
Cystic Fibrosis
Expanded Carrier Panel
Expanded Carrier Screening
Fanconi Anemia Group C
Gaucher's Disease
Genetic Testing, Preconception or Prenatal
GoodStart GeneVu
Inherigen
Inheritest Carrier Screen
Mucolipidosis IV
Niemann Pick Disease Type A
Tay-Sach's Disease

Document History

Status

Date

Action

Revised

05/03/2018

Medical Policy & Technology Assessment Committee (MPTAC) review. In the Position Statement, removed the genetic counseling requirement for cystic fibrosis and spinal muscle atrophy and added a note stating “Genetic counseling should be a component of a decision to perform genetic testing.” Updated Rationale, Coding, References and Websites for Additional Information sections.

Reviewed

03/22/2018

MPTAC review. Updated the References, Websites for Additional Information and History sections.

 

12/27/2017

The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Coding section with 01/01/2018 CPT changes; added codes 81258, 81259, 81269, and 81361-81364 replacing Tier 2 codes for these genes.

 

08/01/2017

Updated Coding section with 08/01/2017 CPT PLA code changes.

Revised

05/04/2017

Medical Policy & Technology Assessment Committee (MPTAC) review. Title changed to Preconception or Prenatal Genetic Testing of a Parent or Prospective Parent. Revised medically necessary position statements to address spinal muscular atrophy, familial dysautonomia, criteria for genetic counseling and the use of a standard panel for cystic fibrosis carrier screening. Minor editing to language in criteria. Added not medically necessary indications for preconception or prenatal genetic screening to determine carrier status of cystic fibrosis. Updated formatting in the Position Statement section. Updated the Rationale, Background/Overview, Definitions, Coding, References, Websites for Additional Information and History sections.

Reviewed

02/02/2017

MPTAC review. Updated formatting in the “Position Statement” section. Updated review date, Background/Overview, References, Websites for Additional Information and History sections.

Reviewed

02/04/2016

MPTAC review. Updated review date, Rationale, Definitions, Background/Overview, References, Index and History sections.

 

01/01/2016

Updated Coding section with 01/01/2016 CPT changes; removed ICD-9 codes.

Reviewed

02/05/2015

MPTAC review. Updated review date, Description/Scope, Rationale, References and History sections.

 

01/01/2015

Updated Coding section with 01/01/2015 CPT changes.

Revised

02/13/2014

Medical Policy & Technology Assessment Committee (MPTAC) review. Additional investigational and not medically necessary position statement added to address preconceptional or prenatal genetic testing using panels of genes (with or without next generation sequencing), including but not limited to whole genome and whole exome sequencing. Updated Rationale, Definitions, Coding, References and History sections.

 

01/01/2014

Updated Coding section with 01/01/2014 CPT descriptor changes.

 

07/01/2013

Updated Coding section with 07/01/2013 CPT changes.

Reviewed

02/14/2013

MPTAC review. Updated review date, History and References sections.

 

01/01/2013

Updated Coding section with 01/01/2013 CPT changes; removed 83890-83914, 88384-88386 deleted 12/31/2012.

Reviewed

02/16/2012

MPTAC review. Updated review date, History and Reference sections.  Updated Coding section with 04/01/2012 HCPCS changes; removed codes S3835, S3837, S3843, S3847, S3848, S3851 deleted 03/31/2012.

 

01/01/2012

Updated Coding section with 01/01/2012 CPT changes.

 

07/13/2011

Updated Coding section; removed S3870 which is now addressed in GENE.00021.

Reviewed

02/17/2011

MPTAC review. Updated review date, History and Reference sections.

 

01/12/2011

Updated Coding section; removed S3865, S3866 which are now addressed in GENE.00017.

Reviewed

02/25/2010

MPTAC review. Updated review date, History and Reference sections. Added note to Description section clarifying that this document is limited to the use of molecular genetic testing and does not provide criteria for karyotype analysis or biochemical testing.

Reviewed

02/26/2009

MPTAC review. Updated review date, History and References section.

New

02/21/2008

MPTAC initial document development. Document created to addresses preconceptional or prenatal genetic testing of a parent or prospective parent, which was formerly addressed in GENE.00001.