The genetic architecture of inherited metabolic disease spans defects in mitochondrial energy generation, carbohydrate and lipid metabolism, amino acid and organic acid pathways, urea cycle function, peroxisomal and lysosomal homeostasis, and related cofactor and transport systems. Germline disruption across these pathways underlies a wide spectrum of presentations, including neonatal metabolic crises, recurrent hypoglycemia, lactic acidosis, cardiomyopathy, myopathy, neurodevelopmental delay, movement disorders, and progressive multisystem organ dysfunction. Early, accurate molecular diagnosis is critical, as many inborn errors of metabolism are amenable to targeted interventions (dietary modification, substrate restriction, cofactor supplementation, toxin scavengers, or enzyme replacement), and delays in recognition can lead to irreversible neurologic injury or death.
PreCheck Health Services’ Comprehensive Metabolic Disease Panel (533 genes) is an advanced targeted exome assay encompassing key genes involved in mitochondrial respiratory chain function, fatty acid β-oxidation, glycogen metabolism, amino acid and organic acid catabolism, urea cycle and nitrogen handling, peroxisomal and lysosomal biogenesis and function, and selected transporters, chaperones, and regulatory factors relevant to systemic metabolic homeostasis. The panel is curated using evidence from ACMG, ClinGen, OMIM, GeneReviews, and current peer-reviewed literature to prioritize genes with well-established gene–disease relationships and actionable phenotypes. This approach enables identification of clinically meaningful germline variants that support definitive diagnosis, refine etiologic classification, guide acute and chronic management (including emergent metabolic decompensation protocols), inform prognosis and transplant decisions, and facilitate cascade testing and reproductive counseling for at-risk relatives.
This assay is designed for patients presenting with or at risk for:
❖ Unexplained neonatal or early-infantile metabolic decompensation (e.g., poor feeding, vomiting, encephalopathy, seizures, lethargy, coma) with lactic acidosis, ketonuria, hyperammonemia, or other abnormal metabolic profiles
❖ Recurrent episodes of hypoglycemia, ketosis, rhabdomyolysis, or metabolic acidosis triggered by fasting, illness, or exertion
❖ Progressive myopathy, exercise intolerance, fatigue, neuropathy, ataxia, or other neuromuscular features suggestive of mitochondrial disease or systemic metabolic dysfunction
❖ Unexplained liver dysfunction or failure (acute, recurrent, or chronic), particularly in infancy or early childhood, with suspicion for fatty acid oxidation disorders, urea cycle defects, or other inborn errors of metabolism
❖ Suspected inborn errors of metabolism based on newborn screening abnormalities, even when confirmatory biochemical testing is equivocal or incomplete
❖ Adults with unexplained multisystem disease (e.g., overlapping neurologic, cardiac, endocrine, and hepatic manifestations) where a late-onset, previously unrecognized metabolic or mitochondrial disorder is suspected
This Comprehensive Metabolic Disease Panel encompasses genes central to mitochondrial energy generation, fatty acid and carbohydrate oxidation, amino acid and organic acid metabolism, urea cycle function, lysosomal and peroxisomal integrity, glycosylation, lipid and lipoprotein handling, and endocrine regulation of energy balance. Genes are organized into major biological and clinical pathways relevant to classic inborn errors of metabolism, mitochondrial disease, monogenic obesity and diabetes, neurometabolic syndromes, and multisystem metabolic disorders encountered from the neonatal period through adulthood.
1.Mitochondrial Respiratory Chain, Dynamics, and mtDNA Maintenance
Genes encoding structural components and assembly factors of the oxidative phosphorylation (OXPHOS) complexes, mitochondrial ribosomal proteins, tRNA synthetases, and factors required for mitochondrial DNA replication, repair, and translation. Defects cause primary mitochondrial encephalomyopathies, cardiomyopathy, liver failure, and multisystem mitochondrial disease:
❖ NDUFA1, NDUFA2, NDUFA6, NDUFA9, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6, NDUFB3, NDUFB8, NDUFB10, NDUFB11, NDUFC2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, COX6B1, COX10, COX15, COX20, UQCRB, UQCRC2, UQCRQ, SDHA, SDHB, SDHD, SDHAF1, SURF1, LRPPRC, TACO1, TTC19, MRPL3, MRPL44, MRPS22, TSFM, TUFM, TARS2, VARS2, CARS2, FARS2, RARS2, MARS2, NARS2, GFM1, GFM2, FASTKD2, LYRM7, NUBPL, MGME1, MTFMT, DNAJC19, DNM1L, MFF, MICU1, MPV17, POLG, POLG2, LONP1, MTPAP
2.Fatty Acid β-Oxidation, Ketone Metabolism, and Carnitine Cycle
Genes involved in mitochondrial and peroxisomal β-oxidation of fatty acids, electron transfer flavoprotein function, ketone body synthesis and utilization, and carnitine transport/shuttling. Pathogenic variants lead to hypoketotic hypoglycemia, cardiomyopathy, rhabdomyolysis, hepatic dysfunction, and fasting intolerance:
❖ ACADM, ACADVL, ACADSB, ACAD8, ACAD9, ACAT1, ACOX1, ECHS1, HADHA, HADHB, HADH, ETFDH, ETFA, ETFB, CPT1A, CPT2, HMGCS2, HMGCL, MLYCD, LPIN1, PNPLA2, LIPE, PLIN1, SLC22A5, SLC25A20, SLC25A32, OXCT1
3.Carbohydrate, Glycogen, and Core Energy Pathways
Genes governing glycolysis, gluconeogenesis, glycogen synthesis and breakdown, and related cytosolic/mitochondrial energy–yielding pathways. Disorders in this group include glycogen storage diseases, disorders of fructose/galactose metabolism, and defects in key gluconeogenic steps causing fasting hypoglycemia and metabolic crises:
❖ G6PC1, G6PC3, GAA, AGL, GBE1, GYS1, GYS2, PYGL, PYGM, PFKM, ALDOA, FBP1, PCK1, PC, PCBD1, TPI1, GCK, GALE, GALK1, GALT, GPD1, TALDO1, TAT, LDHA
4.Amino Acid, Organic Acid, and Urea Cycle Metabolism
Genes encoding enzymes of amino acid catabolism, the tricarboxylic acid (TCA) cycle interfaces, branched-chain ketoacid dehydrogenase complex, and the urea cycle. These loci underlie classic aminoacidopathies, organic acidemias, and hyperammonemic syndromes presenting with metabolic acidosis, neurologic compromise, and liver dysfunction:
❖ ASS1, ASL, ARG1, CPS1, OTC, NAGS, GLUD1, GLDC, GCSH, IVD, MMUT, MCCC1, MCCC2, MCEE, MMAA, MMAB, MMACHC, MMADHC, DLD, DLAT, DHTKD1, D2HGDH, L2HGDH, GCDH, HPD, HOGA1, KYNU, OAT, PRODH, PSAT1, PHGDH, PSPH, UMPS, TYMP, FAH, HMGCL, HIBCH, PAH, BCKDHA, BCKDHB, BCKDK, AUH, ACY1
5.Lysosomal Storage, Peroxisomal, and Organelle Biogenesis Disorders
Genes involved in lysosomal hydrolases and activator proteins, lysosomal trafficking, and peroxisome biogenesis and matrix enzyme function. Defects cause sphingolipidoses, mucopolysaccharidoses, neuronal ceroid lipofuscinoses, cystinosis, and Zellweger spectrum/peroxisomal β-oxidation disorders with multisystem neurologic, skeletal, hepatic, and ocular involvement:
❖ GBA1, GLB1, GLA, ARSA, ARSB, IDUA, IDS, GUSB, SGSH, HGSNAT, HEXA, HEXB, MCOLN1, CLN3, CLN5, CLN6, CLN8, LAMP2, CTSA, CTSD, FUCA1, GM2A, NAGLU, GNS, MAN2B1, MANBA, ASAH1, GALNS, SMPD1, SUMF1, PPT1, MFSD8, CTN, PEX1, PEX2, PEX3, PEX5, PEX6, PEX7, PEX10, PEX11B, PEX12, PEX13, PEX14, PEX16, PEX19, PEX26, ABCD1, ABCD4, AMACR, PHYH, HSD17B4, SCP2, BAAT
6.Congenital Disorders of Glycosylation and GPI-Anchor Biosynthesis
Genes required for N-linked glycosylation, O-linked glycosylation, dolichol/phosphomannose handling, and glycosylphosphatidylinositol (GPI) anchor synthesis and remodeling. Pathogenic variants produce multisystem congenital disorders of glycosylation (CDG) with developmental delay, hypotonia, coagulopathy, liver disease, cardiomyopathy, and dysmorphic features:
❖ ALG1, ALG2, ALG3, ALG6, ALG8, ALG9, ALG11, ALG12, ALG13, ALG14, DOLK, DPAGT1, DPM1, DPM2, DPM3, MAN1B1, MGAT2, MPI, PMM2, PGM1, RFT1, SSR4, ST3GAL3, ST3GAL5, SRD5A3, PIGA, PIGL, PIGN, PIGO, PIGT, PIGV, PGAP2, PGAP3
7.Lipid, Lipoprotein, Bile Acid, and Cholesterol Metabolism
Genes controlling triglyceride and cholesterol transport, lipoprotein assembly and clearance, bile acid synthesis and secretion, and adipose tissue lipid mobilization. Disorders include familial hypercholesterolemia, sitosterolemia, chylomicron retention disease, bile acid synthetic defects, and lipodystrophy/steatohepatitis syndromes:
❖ ABCA1, ABCB4, ABCB11, ABCG5, ABCG8, APOA1, APOA5, APOB, APOC2, LPL, LDLR, LDLRAP1, PCSK9, MTTP, BAAT, CYP7B1, CYP27A1, HSD3B7, GPIHBP1, LPIN1, PNPLA2, PLIN1, LIPE, SAR1B, LMNA, PPARG, LCAT
8.Endocrine, Obesity, Monogenic Diabetes, and Systemic Metabolic Regulation
Genes affecting pancreatic β-cell function, insulin secretion, hepatic transcriptional control of glucose homeostasis, central energy balance pathways, and systemic iron and micronutrient handling. These loci underlie monogenic diabetes, severe early-onset obesity, lipodystrophy, and iron overload/deficiency syndromes:
❖ ABCC8, KCNJ11, GCK, HNF1A, HNF1B, HNF4A, PCSK1, MC4R, LEP, LEPR, POMC, SIM1, PPARG, LMNA, HFE, TFR2, HAMP, HJV, SLC40A1, SLC39A4, VKORC1
9.Membrane Transporters and Other Multisystem Metabolic Syndromes
A broad group of solute carriers, ion channels, and related transport proteins that mediate cellular uptake and export of sugars, amino acids, organic acids, metals, and other small molecules, as well as signaling components that produce complex neurometabolic or hepatorenal phenotypes:
❖ SLC2A1, SLC2A2, SLC3A1, SLC6A8, SLC6A19, SLC7A7, SLC7A9, SLC12A3, SLC13A5, SLC16A1, SLC17A5, SLC22A5, SLC25A1, SLC25A3, SLC25A4, SLC25A12, SLC25A13, SLC25A15, SLC25A19, SLC25A20, SLC25A22, SLC25A38, SLC25A46, SLC30A10, SLC33A1, SLC35A1, SLC35A2, SLC35C1, SLC37A4, SLC40A1, SLC46A1, SLC52A2, SLC52A3, SLC5A1, FXYD2, TRPM6, TRPM7, SC5D, SI, LCT, MAGT1, VIPAS39, VPS33B, RAI1, SACS,
Genes Analyzed 533 Metabolism disease-related genes.
Technology Platform Illumina NGS (Hybrid-Capture Target Enrichment).
Coverage Metrics >98% bases at ≥20× read depth.
Variant Types Detected SNVs and small indels (≤20 bp) within coding exons ±10 bp intronic boundaries.
Reference Genome GRCh38/hg38.
Bioinformatics Pipeline SeqOne™, ACMG/AMP compliant.
Confirmatory Testing Sanger sequencing or orthogonal method as indicated.
Turnaround Time ~10 calendar days.
Quality Metrics Read quality ≥Q30; allelic balance ≥0.3; minimum coverage 20×.
1.Congenital and Early-Onset Metabolic Disease
❖ Clarify the etiology of neonatal and infantile metabolic crises presenting with acidosis, hyperammonemia, hypoglycemia, lactic acidosis, or encephalopathy
❖ Distinguish primary inborn errors of metabolism from secondary/metabolic mimics (sepsis, hypoxic–ischemic injury, liver failure of other causes)
❖ Support early initiation of targeted interventions (dietary restriction, special formulas, cofactor therapy, toxin scavengers, dialysis, or transplant referral) and structured long-term follow-up
2.Recurrent Metabolic Decompensation, Hypoglycemia, and Rhabdomyolysis
❖ Define molecular causes of recurrent hypoketotic hypoglycemia, exertional rhabdomyolysis, cardiomyopathy, or fasting intolerance (e.g., fatty acid oxidation disorders, glycogen storage diseases)
❖ Refine acute illness protocols, fasting and exercise restrictions, emergency department action plans, and perioperative management strategies
❖ Prevent misdiagnosis as “isolated” hepatic, cardiac, or muscle disease and reduce morbidity from repeated decompensations
3.Neurometabolic and Mitochondrial Disorders
❖ Identify underlying mitochondrial, peroxisomal, lysosomal, or amino acid/organic acid defects in patients with developmental delay, epilepsy, regression, movement disorders, ataxia, or stroke-like episodes
❖ Guide neuroimaging, cardiac and ophthalmologic surveillance, and consideration of disease-modifying options (e.g., vitamin/cofactor regimens, enzyme replacement, substrate reduction where applicable)
❖ Provide prognostic information that helps distinguish static from progressive disorders and informs rehabilitation, education, and supportive care planning
4.Newborn Screening Follow-up, Family Counseling, and Cascade Testing
❖ Confirm, refine, or refute presumptive diagnoses from abnormal newborn screening when biochemical results are equivocal or incomplete
❖ Enable targeted testing of relatives once a pathogenic or likely pathogenic variant is identified, clarifying carrier status and recurrence risk
❖ Integrate germline results with biochemical profiles, imaging, and clinical history to build durable, patient-centered care plans and coordinated transition from pediatric to adult metabolic services
Comprehensive Metabolic Disease testing provides clinically actionable information across medical genetics, metabolism, neonatology, pediatrics, neurology, hepatology, cardiology, endocrinology, and internal medicine, directly influencing diagnosis, risk assessment, surveillance, and treatment strategies.
Risk Stratification and Diagnostic Clarification Identify pathogenic or likely pathogenic variants underlying inborn errors of metabolism, mitochondrial disease, fatty acid oxidation defects, glycogen storage disorders, amino acid and organic acidemias, urea cycle defects, peroxisomal and lysosomal disorders, monogenic forms of diabetes, dyslipidemia, and obesity. Distinguish primary metabolic conditions from secondary or acquired etiologies, refine differential diagnoses generated by abnormal biochemical profiles or imaging, and convert “probable” or “suspected” metabolic disease into a definitive, gene-based diagnosis.
Family Risk Assessment, Cascade Testing, and Reproductive Counseling
Clarify recurrence risk for families, identify at-risk relatives, and support targeted cascade testing once a familial variant is known. Enable early surveillance and anticipatory guidance in gene-positive but asymptomatic individuals (e.g., during intercurrent illness or stress), and inform reproductive planning, including options such as prenatal or preimplantation genetic testing when appropriate.
Treatment Selection and Therapeutic Optimization
Use genotype to refine acute and chronic management, including dietary restrictions or supplementation (e.g., protein, long-chain fat, specific sugars), emergency decompensation protocols, cofactor/vitamin therapy, enzyme replacement, substrate reduction, or chaperone therapies where available. Inform decisions about intensity of monitoring, ICU thresholds, transplant referral (liver, heart, combined organ), and choice or avoidance of medications that may precipitate metabolic crises, myopathy, or organ decompensation in specific genetic backgrounds.
Integrated Longitudinal Metabolic Care
Support multidisciplinary teams (metabolic genetics, neurology, cardiology, hepatology, nephrology, endocrinology, nutrition, primary care) in building unified, gene-informed care plans that coordinate biochemical monitoring, imaging, dietetic support, emergency action plans, and transition from pediatric to adult services over the patient’s lifespan. Provide a durable framework for adapting management as guidelines, therapies, and variant classifications evolve, and for managing complex, multisystem metabolic disorders within affected families.
This Comprehensive Metabolic Disease Panel is best used as part of a multi-dimensional diagnostic strategy, often in combination with:
Pharmacogenetics Testing (for drug metabolism and gene-drug interactions)
❖ Match treatments to the patient’s metabolic phenotype (e.g., CYP2D6, CYP2C19, CYP3A5, CYP2C9), reducing the risk of adverse drug reactions and improving efficacy.
Together, these tools enable precision medicine teams to offer a fully customized, data-driven treatment plan for each patient.
Germline testing for inherited metabolic disease is now a critical component of precision care, allowing clinicians to define the molecular basis of neonatal metabolic crises, recurrent hypoglycemia and rhabdomyolysis, neurometabolic and mitochondrial syndromes, lysosomal and peroxisomal disorders, and monogenic forms of diabetes, dyslipidemia, and obesity with far greater resolution than clinical and biochemical assessment alone. With a rigorously curated gene panel, high analytic performance, and clinically validated interpretation, PreCheck Health Services provides the genomic insights necessary to refine diagnosis, tailor acute decompensation and chronic management protocols, inform transplant and medication decisions, and support cascade testing and reproductive counseling. This integrated approach enables earlier, more precise, and more preventive management across the full spectrum of hereditary and familial metabolic conditions, improving outcomes for affected patients and at-risk relatives.
The Comprehensive Metabolic Disease Panel is designed to detect single-nucleotide variants (SNVs) and small insertions and deletions in 533 genes associated with inherited metabolic disorders. Targeted regions for this panel include the coding exons and 10 bp intronic sequences immediately to the exon-intron boundary of each coding exon in each of these genes. Extracted patient DNA is prepared using targeted hybrid capture, assignment of a unique index, and sequencing via Illumina sequencing by synthesis (SBS) technology. Data is aligned using the human genome build GRCh38. Variant interpretation is performed according to current American College of Medical Genetics and Genomics (ACMG) professional guidelines for the interpretation of germline sequence variants using SeqOne Pipeline.
ABCA1, ABCB4, ABCB11, ABCC8, ABCD1, ABCD4, ABCG5, ABCG8, ABHD5, ACAD8, ACAD9, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACOX1, ACY1, AGL, AKR1D1, ALDH4A1, ALDH5A1, ALDH6A1, ALDH7A1, ALDH18A1, ALDOA, ALDOB, ALG1, ALG2, ALG3, ALG6, ALG8, ALG9, ALG11, ALG12, ALG13, ALG14, AMACR, AMT, APOA1, APOA5, APOB, APOC2, APOE, ARG1, ARSA, ARSB, ASAH1, ASL, ASPA, ASS1, ATP7A, ATP7B, AUH, BAAT, BCKDHA, BCKDHB, BCKDK, BCS1L, BOLA3, BTD, CARS2, CASR, CBS, CD320, CLN3, CLN5, CLN6, CLN8, COQ2, COQ4, COQ6, COQ9, COX6B1, COX10, COX15, COX20, COXFA4, CP, CPS1, CPT1A, CPT2, CTNS, CTSA, CTSD, CYP7B1, CYP27A1, D2HGDH, DGUOK, DHCR7, DHCR24, DHFR, DHTKD1, DLAT, DLD, DNAJC19, DNM1L, DOLK, DPAGT1, DPM1, DPM2, DPM3, DPYD, DPYS, EARS2, EBP, ECHS1, ETFA, ETFB, ETFDH, ETHE1, FAH, FARS2, FASTKD2, FBP1, FECH, FH, FKRP, FKTN, FOXRED1, FTCD, FTL, FUCA1, FUT8, FXYD2, G6PC1, G6PC3, GAA, GALE, GALK1, GALNS, GALNT2, GALT, GAMT, GATM, GBA1, GBE1, GCDH, GCH1, GCK, GCLC, GCSH, GFER, GFM1, GFM2, GFPT1, GK, GLA, GLB1, GLDC, GLRB, GLRX5, GLS, GLUD1, GLUL, GLYCTK, GM2A, GMPPB, GNE, GNPTAB, GNPTG, GNS, GPD1, GPHN, GPIHBP1, GSS, GTPBP3, GUSB, GYG1, GYS1, GYS2, HADH, HADHA, HADHB, HAMP, HEXA, HEXB, HFE, HGD, HGSNAT, HIBCH, HJV, HLCS, HMBS, HMGCL, HMGCS2, HNF1A, HNF1B, HNF4A, HOGA1, HPD, HPRT1, HPS1, HSD3B7, HSD17B4, HSD17B10, HTRA2, HYAL1, IARS2, IBA57, IDH2, IDS, IDUA, IER3IP1, INSR, ISCA2, ISCU, ITPA, IVD, KCNJ11, KYNU, L2HGDH, LAMP2, LARS2, LCAT, LCT, LDHA, LDLR, LDLRAP1, LEP, LEPR, LETM1, LIAS, LIPA, LIPE, LIPT1, LMBRD1, LMNA, LONP1, LPIN1, LPL, LRPPRC, LYRM7, MAGT1, MAN1B1, MAN2B1, MANBA, MAOA, MARS2, MAT1A, MC4R, MCCC1, MCCC2, MCEE, MCOLN1, MDH2, MFF, MFSD8, MGAT2, MGME1, MICU1, MLYCD, MMAA, MMAB, MMACHC, MMADHC, MMUT, MOCOS, MOCS1, MOCS2, MOGS, MPC1, MPDU1, MPI, MPV17, MRPL3, MRPL44, MRPS22, MSMO1, MTFMT, MTO1, MTPAP, MTR, MTRR, MTTP, MVK, NADK2, NAGA, NAGLU, NAGS, NARS2, NDUFA1, NDUFA2, NDUFA6, NDUFA9, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6, NDUFB3, NDUFB8, NDUFB10, NDUFB11, NDUFC2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NEU1, NFS1, NFU1, NGLY1, NHLRC1, NNT, NPC1, NPC2, NSDHL, NT5C3A, NUBPL, OAT, OCRL, OGDH, OPA1, OPA3, OTC, OXCT1, PAH, PANK2, PARS2, PC, PCBD1, PCCA, PCCB, PCK1, PCSK1, PCSK9, PDHA1, PDHB, PDHX, PDK3, PDP1, PDSS1, PDSS2, PEPD, PET100, PEX1, PEX2, PEX3, PEX5, PEX6, PEX7, PEX10, PEX11B, PEX12, PEX13, PEX14, PEX16, PEX19, PEX26, PFKM, PGAM2, PGAP2, PGAP3, PGK1, PGM1, PHGDH, PHKA1, PHKA2, PHKB, PHKG2, PHYH, PIGA, PIGL, PIGN, PIGO, PIGT, PIGV, PLA2G6, PLIN1, PMM2, PMPCA, PNP, PNPLA2, PNPO, PNPT1, POLG, POLG2, POMC, POR, PPARG, PPM1K, PPOX, PPT1, PRKAG2, PRODH, PRPS1, PSAP, PSAT1, PSPH, PTF1A, PTPRF, PTS, PUS1, PYGL, PYGM, QDPR, RAI1, RARS2, RBCK1, RFT1, RMND1, RNASEH2A, RPIA, RRM2B, RYR1, SACS, SAR1B, SARS2, SC5D, SCO1, SCO2, SCP2, SDHA, SDHAF1, SDHB, SDHD, SEC23B, SERAC1, SERPINA1, SFXN4, SGSH, SI, SIM1, SKIC3, SLC2A1, SLC2A2, SLC3A1, SLC5A1, SLC6A8, SLC6A9, SLC6A19, SLC7A7, SLC7A9, SLC12A3, SLC13A5, SLC16A1, SLC17A5, SLC19A1, SLC19A2, SLC19A3, SLC22A5, SLC25A1, SLC25A3, SLC25A4, SLC25A12, SLC25A13, SLC25A15, SLC25A19, SLC25A20, SLC25A22, SLC25A38, SLC25A46, SLC30A10, SLC33A1, SLC35A1, SLC35A2, SLC35C1, SLC37A4, SLC39A4, SLC40A1, SLC46A1, SLC52A2, SLC52A3, SMPD1, SPG7, SPR, SPTLC1, SPTLC2, SRD5A3, SSR4, ST3GAL3, ST3GAL5, STT3A, SUCLA2, SUCLG1, SUMF1, SUOX, SURF1, TACO1, TAFAZZIN, TALDO1, TARS2, TAT, TCN2, TFR2, TH, TIMM8A, TK2, TMEM70, TMEM126A, TMEM165, TOP3A, TPI1, TPK1, TPP1, TRIM37, TRIT1, TRMU, TRNT1, TRPM6, TRPM7, TSFM, TTC19, TTPA, TUFM, TYMP, UMPS, UPB1, UQCRB, UQCRC2, UQCRQ, UROD, UROS, VARS2, VIPAS39, VKORC1, VPS33B, WFS1, XDH, XYLT2, YARS2, ZMPSTE24
This test aims to detect all clinically relevant variants within the coding regions of the genes evaluated. Pathogenic and likely pathogenic variants detected in these genes should be confirmed by orthogonal methods. Detected genetic variants classified as benign, likely benign, or of uncertain significance are not included in this report. Homopolymer regions and regions outside of the coding regions cannot be captured by the standard NGS target enrichment protocols. Currently, the assay does not detect large deletions and duplications. This analysis also cannot detect pathogenic variants within regions that were not analyzed (e.g., introns, promoter and enhancer regions, long repeat regions, and mitochondrial sequence). This assay is not designed to detect mosaicism and is not designed to detect complex gene rearrangements or genomic aneuploidy events. It is important to understand that there may be variants in these genes undetectable using current technology. Additionally, there may be genes associated with metabolism whose clinical association has not yet been definitively established. The test may therefore not detect all variants associated with metabolic disease. The interpretation of variants is based on our current understanding of the genes in this panel and is based on current ACMG professional guidelines for the interpretation of germline sequence variants. Interpretations may change over time as more information about the genes in this panel becomes available. Qualified health care providers should be aware that future reclassifications of genetic variants can occur as ACMG guidelines are updated. Factors influencing the quantity and quality of extracted DNA include, but are not limited to, collection technique, the amount of buccal epithelial cells obtained, the patient’s oral hygiene, and the presence of dietary or microbial sources of nucleic acids and nucleases, as well as other interfering substances and matrix-dependent influences. PCR inhibitors, extraneous DNA, and nucleic acid-degrading enzymes may adversely affect assay results.
This laboratory-developed test (LDT) was developed, and its performance characteristics were determined by PreCheck Health Services, Inc. This test was performed at PreCheck Health Services, Inc. (CLIA ID: 10D2210020 and CAP ID: 9101993), which is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as qualified to perform high complexity testing.
This assay has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Clearance or approval by the FDA is not required for the clinical use of this analytically and clinically validated laboratory-developed test. This assay has been developed for clinical purposes, and it should not be regarded as investigational or for research.
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