Test Details


Carrier screening by analyzing 48 genes for more than 2,300 pathogenic variants associated with more than 47 autosomal recessive or X-linked disorders including genes for fragile X syndrome, spinal muscular atrophy, and diseases specific to individuals of Ashkenazi Jewish descent.

Special Instructions

Test orders must include an attestation that the provider has the patient's informed consent for genetic testing. See sample physician office consent form: Consent for Genetic Testing. Call Integrated Genetics at 855-422-2557 to obtain access to genetic counseling.

Test Includes

Screening for 48 genes, including fragile X carrier screening and spinal muscular atrophy (SMA) carrier screening. This test includes: ABCC8, ADAMTS2, AGL, ARSA, ASPA, ATM, ATP7B, BBS2, BCKDHA, BCKDHB, BLM, CFTR, CLRN1, COL4A3, CPT2, CTNS, DHCR7, DHDDS, DLD, FAH, FANCC, FKTN, FMR1, G6PC, GALT, GBA, HBA1, HBA2, HBB, HEXA, IKBKAP, MCOLN1, MEFV, MPL, MTTP, NEB, PAH, PCDH15, PEX2, PHGDH, PKHD1, PEX6, PMM2, SMPD1, TMEM216, SLC35A3, SMN1 and SUMF1.


SMN1 copy number analysis does not detect individuals who are carriers of SMA as a result of germline mosaicism; or small intragenic mutations within the SMN1 gene; or mutations in genes other than SMN1. Individuals with one copy of SMN1 are predicted to be carriers of SMA; those with two or more copies have a reduced carrier risk. For individuals with two copies of SMN1, the presence or absence of the variant c.*3+80T>G correlates with an increased or decreased risk, respectively, of being a silent carrier (2+0).1,2

Technologies used do not detect germline mosaicism and do not rule out the presence of large chromosomal aberrations, including rearrangements, or variants in regions or genes not included in this test, or possible inter/intragenic interactions between variants. Variant classification and/or interpretation may change with time if more information becomes available. False-positive or false-negative results may occur for reasons that include: genetic variants, technical handling, blood transfusions, bone marrow transplantation, mislabeling of samples, or erroneous representation of family relationships.

This test was developed and its performance characteristics determined by Esoterix Genetic Laboratories LLC. It has not been cleared or approved by the Food and Drug Administration.


Next generation sequencing (NGS): Genomic regions of interest are selected using the Agilent® SureSelectXT® hybridization capture method for target enrichment and sequenced via the Illumina® next generation sequencing platform. Sequencing reads are aligned with the human genome reference GRCh37/hg19 build. Targeted regions are sequenced to at least 200X mean base coverage with a minimum of 99% of bases at > or = 20X coverage. Analytical sensitivity is estimated to be >99% for single nucleotide variants and small insertions/deletions (<5 bp).

Alpha-thalassemia: Analysis of the alpha-globin (HBA) gene cluster is performed by multiplex ligationdependent amplification (MLPA). Variants included in the analysis are the Constant Spring non-deletion variant and the following deletions: -alpha3.7, -alpha4.2, -alpha20.5, --SEA, --FIL, --THAI, --MED, and the HS-40 regulatory region. This MLPA analysis does not detect other variants in the alpha-globin genes or variants in the beta-globin gene and may not detect the co-occurrence of a deletion and a duplication. Analytical sensitivity is estimated to be >99% for the targeted variants.

Spinal muscular atrophy: The copy number of SMN1 exon 7 is assessed relative to internal standard reference genes by quantitative polymerase chain reaction (qPCR). A mathematical algorithm calculates 0, 1, 2 and 3 copies with statistical confidence. When no copies of SMN1 are detected, the primer and probe binding sites are sequenced to rule out variants that could interfere with copy number analysis and SMN2 copy number is assessed by digital droplet PCR analysis relative to an internal standard reference gene. Individuals with one copy of SMN1 are predicted to be carriers of SMA; those with two or more copies have a reduced carrier risk. For carrier screening, when two copies of SMN1 are detected, allelic discrimination qPCR targeting c.*3+80T>G in SMN1 is performed. The presence or absence of c.*3+80T>G correlates with an increased or decreased risk, respectively, of being a silent carrier (2+0).1,2

Fragile X syndrome: DNA is amplified by the polymerase chain reaction (PCR) to determine the size of the CGG repeat region within the FMR1 gene. PCR products are generated using a fluorescence labeled primer and sized by capillary gel electrophoresis. If indicated, Southern blot analysis is performed by hybridizing the probe StB12.3 to EcoRI- and EagI-digested DNA. The analytical sensitivity of both Southern blot and PCR analyses is 99% for expansion mutations in the FMR1 +/- one for repeats less than 60, and +/- two to four for repeats in the 60 - 120 range. For repeats greater than 120, the accuracy is +/- 10%. If 55-90 trinucleotide repeats are detected in carrier screening females, a PCR assay targeting AGG sequences within the CGG repeats is performed to assess the number and position of AGG interruptions.

Reported variants: Pathogenic and likely pathogenic variants are reported. Nondeletion variants are specified using the numbering and nomenclature recommended by the Human Genome Variation Society (HGVS). Variants of uncertain significance and benign variants are not reported. Variant classification and confirmation are is consistent with ACMG standards and guidelines.3,4 Detailed variant classification information is available upon request.

Specimen Requirements

Information on collection, storage, and volume


Whole blood


8.5 mL


Yellow-top (ACD-A) tube (preferred) or lavender-top (EDTA) tube; yellow-top (ACD-B) tube is not acceptable

Storage Instructions

Maintain specimen at room temperature or refrigerate at 4°C.

Causes for Rejection

Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container; blood specimens more than four days post draw