Test Details

Use

Full gene sequencing is available for the majority of genes included in the Inheritest® NGS panels. See related Inheritest® test codes: Inheritest® Carrier Screen, Comprehensive Panel (144 Genes) [451950]; or Inheritest® Carrier Screen, Ashkenazi Jewish Panel (48 Genes) [451920]; or Inheritest® Carrier Screen, Society-guided Panel (14 Genes) [451960].

For HBA1 and HBA2 (alpha-thalassemia) see α-Thalassemia, DNA Analysis [511172]; for SMN1 see Spinal Muscular Atrophy (SMA) Carrier Testing [450010]; and for FMR1 see Fragile X Syndrome, PCR With Reflex to Southern Blot [511919].

Special Instructions

For prenatal testing: LabCorp clients call 800-345-4363, Integrated Genetics clients call 800-848-4436 to speak to a laboratory genetic coordinator before collecting specimens. In some circumstances, specimens from other family members may be required. All prenatal specimens (including cord blood) must be accompanied by a maternal blood or mouthwash specimen for analysis of the specimen for possible maternal cell contamination.

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.

Indicate the specific gene(s) to be analyzed on the test request form. Failure to indicate the gene(s) will result in testing delays.

Test Includes

Full gene sequencing for any one of the following genes: ABCC8, ACADM, ACADVL, ACAT1, ADA, ADAMTS2, AGA, AGL, AGXT, ALDH3A2, ALDOB, ALPL, AMT, ARSA, ARSB, ASL, ASPA, ASS1, ATM, ATP7B, BBS1, BBS2, BBS10, BCKDHA, BCKDHB, BCS1L, BLM, CBS, CFTR, CLN3, CLN5,CLN8, CLRN1, COL4A3, COX15, CPS1, CPT2, CTNS, CTSA, DHCR7, DHDDS, DLD, DMD, DPYD,ERCC5, ETHE1, FAH, FANCC, FKTN, FOXRED1, FUCA1, G6PC, GAA, GALC, GALNS, GAMT, GALT, GBA, GCDH, GLB1, GLDC, GNPTAB, GNS, GRHPR, GSS, GUSB, HADHA, HBB, HEXA, HEXB, HGSNAT, HLCS, HMGCL, HSD17B4, IDS, IDUA, IL2RG, IKBKAP, LAMA3, LAMB3, LAMC2, LRPPRC, MAN2B1, MANBA, MCOLN1, MEFV, MMAA, MMAB, MMACHC, MPL, MTTP, MUT, NAGLU, NBN, NDUFAF2, NDUFS4, NDUFS7, NDUFV1, NEB, NEU1, NPC1, NPC2, NPHS1, NPHS2, OTC, PAH, PCCA, PCCB, PDHA1, PCDH15, PEX1, PEX2, PEX6, PEX7, PEX10, PEX12, PEX26, PKHD1, PHGDH, PMM2, PPT1, RMRP, SACS, SLC12A6, SLC17A5, SLC26A2, SLC37A4, SMPD1, TMEM216, TPP1, SGSH, SLC22A5, SLC25A20, SLC35A3, SUMF1, SURF1, TTPA, VPS13B, XPA and XPC.

Deletion/Duplication analysis for HBA1 and HBA2 can be ordered using this test code. Full gene sequencing cannot be performed.

Associated diseases include: Abetalipoproteinemia; Adenosine deaminase deficiency; Alpha-thalassemia; Alphamannosidosis; Alport syndrome; Andermann syndrome; Argininosuccinic aciduria; Arthrogryposis, mental retardation, and seizures (AMRS); Aspartylglucosaminuria; Ataxia with vitamin E deficiency; Ataxia-telangiectasia; Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS); Bardet-Biedl syndrome; Beta hemoglobinopathies, includes sickle cell disease and beta thalassemias; Beta-mannosidosis; Bloom syndrome; Canavan disease; Carbamoyl phosphate synthetase I deficiency; Carnitine palmitoyltransferase II deficiency; Carnitine-acylcarnitine translocase deficiency; Cartilage-hair hypoplasia; Citrullinemia type I; Cobalamin C disease; Cohen syndrome; Congenital amegakaryocytic thrombocytopenia; Congenital disorder of glycosylation type 1a; Cystic fibrosis; Cystinosis; D-bifunctional protein deficiency; Dihydrolipoamide dehydrogenase deficiency; Dihydropyrimidine dehydrogenase deficiency; Ehlers-Danlos syndrome type VIIC; Ethylmalonic encephalopathy; Familial dysautonomia; Familial hyperinsulinism; Familial Mediterranean fever; Fanconi anemia group C; Fucosidosis; Galactosemia; Galactosialidosis; Gaucher disease; Glutaric acidemia type 1; Glutathione synthetase deficiency; Glycine encephalopathy; Glycogen storage disease type Ia; Glycogen storage disease type Ib; Glycogen storage disease type III; GM1 gangliosidosis and mucopolysaccharidosis type IVB; GRACILE syndrome; Guanidinoacetate methyltransferase deficiency; Hereditary fructose Intolerance; HMGCoA lyase deficiency; Holocarboxylase synthetase deficiency; Homocystinuria; Hypophosphatasia, autosomal recessive; Joubert syndrome 2; Junctional epidermolysis bullosa; Krabbe disease; Leigh syndrome, autosomal recessive; Leigh syndrome, French Canadian type; Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency; Maple syrup urine disease type 1A; Maple syrup urine disease type 1B; Medium-chain acyl-CoA dehydrogenase deficiency; Metachromatic leukodystrophy; Methylmalonic acidemia; Mucopolysaccharidosis type IIIA; Mucopolysaccharidosis type IIIB; Mucopolysaccharidosis type IIIC; Mucopolysaccharidosis type IIID; Mucopolysaccharidosis type IV A; Mucopolysaccharidosis type VI; Mucopolysaccharidosis type VII; Multiple sulphatase deficiency; Nemaline myopathy; Nephrotic syndrome; Nephrotic syndrome, Finnish type; Neuronal ceroid-lipofuscinosis; Niemann-Pick disease type C; Niemann-Pick disease types A and B; Nijmegen breakage syndrome; Ornithine transcarbamylase deficiency; Phenylalanine hydroxylase deficiency, includes phenylketonuria (PKU); Phosphoglycerate dehydrogenase deficiency; Polycystic kidney disease, autosomal recessive; Pompe disease; Primary hyperoxaluria type 1; Primary hyperoxaluria type 2; Propionic acidemia; Pyruvate dehydrogenase deficiency; Retinitis pigmentosa 59; Rhizomelic chondrodysplasia punctata type 1; Salla disease; Sandhoff disease; Sialidosis; Sjogren-Larsson syndrome; Smith-Lemli-Opitz syndrome; Sulfate transporter-related osteochondrodysplasias, includes achondrogenesis type 1B, atelosteogenesis type 2, diastrophic dysplasia, and recessive multiple epiphyseal dysplasia; Systemic primary carnitine deficiency; Tay-Sachs disease; Tyrosinemia type 1; Usher syndrome type IF; Usher syndrome type IIIA; Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD); Walker-Warburg syndrome; Wilson disease; Xeroderma pigmentosum; X-linked severe combined Immunodeficiency (SCID); Zellweger spectrum disorder.

Limitations

NGS does not detect germline mosaicism and does 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. In-frame and out-of-frame deletions in the DMD gene cannot be distinguished by this analysis, which does not determine precise breakpoints. A deletion or duplication of exons in the DMD gene is identified when more than >60% of an exon has an aberrant copy number. Variant classification and/or interpretation may change over time if more information becomes available. False positive or false negative results may occur for reasons that include: rare genetic variants, sex chromosome abnormalities, pseudogene interference, blood transfusions, bone marrow transplantation, somatic or tissue-specific mosaicism, mislabeled samples, or erroneous representation of family relationships.

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

Methodology

Next generation sequencing (NGS): Genomic regions of interest are selected using the AgilentrSureSelectXT® 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 greater than or equal to 20X coverage. Analytical sensitivity is estimated to be >99% for single nucleotide variants and small insertions/deletions (<5 bp).

Reported vartiants: Pathogenic and likely pathogenic variants and variants of uncertain significance (VUS) are reported. Non-deletion variants are specified using the numbering and nomenclature recommended by the Human Genome Variation Society (HGVS). Benign variants are not reported. Variant classifications and confirmation are consistent with ACMG standards and guidelines.1,2 Detailed variant classification information is available upon request. A variant of uncertain significance (VUS) should not be used in clinical decision making; a VUS is classified based on inadequate or conflicting evidence regarding its pathogenicity or clinical relevance.

Related Documents

Specimen Requirements

Information on collection, storage, and volume

Specimen

Whole blood, amniotic fluid, chorionic villus sample (CVS), cultured amniocytes, cultured villi. Submission of maternal blood is required for analysis of Maternal Cell Contamination (511402), which should be ordered on a separate test request form.

Volume

8.5 mL whole blood; amniotic fluid: 20 cc, CVS: 20 mg, or amniotic fluid and CVS culture: two confluent flasks amniotic fluid: 20 cc, CVS: 20 mg, or amniotic fluid and CVS culture: two confluent flasks

Container

Yellow-top (ACD-A) tube or lavender-top (EDTA) tube; for prenatal specimens: sterile plastic conical tube or two confluent T-25 flasks

Storage Instructions

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

Causes for Rejection

Frozen specimen; quantity not sufficient for analysis; improper container