The genetic landscape of the human nervous system plays a critical role in shaping susceptibility to neurological disease, variability in clinical presentation, and response to treatment. Neurogenetic testing provides clinicians with a precise view of the molecular mechanisms underlying disorders of the brain, peripheral nerves, and neuromuscular system, allowing for targeted diagnosis, therapy selection, and long-term management.
PreCheck Health Services’ Comprehensive Neurology Panel (203 genes) represents an advanced targeted exome assay designed to evaluate the genetic determinants of epilepsy, neuromuscular disease, leukodystrophies, hereditary neuropathies, and neurodegenerative conditions. The panel is curated using evidence-based resources including ACMG, ClinGen, OMIM, GeneReviews, and current peer-reviewed literature, enabling the identification of clinically actionable variants that directly inform treatment decisions, surveillance strategies, and family risk assessment.
❖ Epilepsy with unexplained onset, drug resistance, or features suggestive of genetic channelopathy
❖ Neuromuscular disorders, including hereditary myopathies, congenital myasthenic syndromes, and muscular dystrophies
❖ Peripheral neuropathies, such as hereditary motor–sensory neuropathies and axonal or demyelinating neuropathies
❖ Hereditary ataxias, spastic paraplegias, or movement disorders with unclear etiology
❖ Early-onset neurodegenerative disorders, including hereditary parkinsonism and ALS-spectrum syndromes
❖ Familial clustering of neurological conditions suggestive of inherited risk
❖ Patients with complex or atypical neurological presentations where genetic causes may guide management, prognosis, or therapy selection
1.Ion Channels and Neuronal Excitability
Genes regulating membrane excitability, action potential generation, and synaptic transmission:
❖ SCN1A, SCN1B, SCN2A, SCN8A, KCNA1, KCNC3, KCNQ2, GABRG2, PRRT2, PRKCG, GRID2, GRIN2A
2.Synaptic Function and Neurotransmission
Genes involved in synaptic vesicle release, synaptic maintenance, and neuronal communication:
❖ STXBP1, SYNGAP1, SYNJ1, DNM2, DNAJC5, DNAJC6, APP, PNKD, CAPN1, FIG4, SNCA, GNB4, GNAL
3.Axonal Transport and Motor Neuron Integrity
Key genes affecting axon structure, motor neuron survival, and cytoskeleton function:
❖ DYNC1H1, KIF5A, SPAST, SPG7, ATL1, REEP1, BSCL2, NEFL, NEK1, TUBA4A, VCP, ANXA11, OPTN
4.Mitochondrial Function and Oxidative Phosphorylation
Genes mediating mitochondrial DNA maintenance, respiratory chain function, and energy metabolism:
❖ POLG, POLG2, TWNK, MPV17, AARS2, MGME1, SUCLA2, SUCLG1, COX10, SCO1, SCO2, COQ2, COQ8A, PDSS2, TYMP, DGUOK, GAA, G6PC, ALDH7A1
5.Myelin Biology and Leukodystrophies
Genes contributing to myelin formation, maintenance, and white matter integrity:
❖ ARSA, GALC, PLP1, PMP22, MPZ, LMNB1, CST3, GBE1, HINT1, HSPB1, HSPB8, SLC52A2, SLC52A3, SOD1
6.Hereditary Ataxias, Spastic Paraplegias, and Movement Disorders
Genes associated with cerebellar dysfunction, axon degeneration, and movement abnormalities:
❖ CACNA1A, ITPR1, SPTBN2, TTBK2, SPG11, SPTLC1, SPTLC2, SACS, PNKD, TOR1A, THAP1
7.Neurodegenerative and Dementia-Associated Genes
Genes implicated in ALS, Parkinson’s disease, frontotemporal dementia, and related disorders:
❖ C19orf12, TARDBP, FUS, TREM2, GRN, MAPT, PSEN1, PSEN2, CHMP2B, LRRK2, UBQLN2, ANG, HNRNPA1, HNRNPA2B1, SQSTM1
8.DNA Repair, Chromatin, and Transcription Factors
Genes essential for genome maintenance, transcriptional regulation, and neuronal development:
❖ C21orf2, MECP2, DNMT1, CHD2, CHMP2B, SETX, FANCC, ZEB2, TCF4, EGR2, TPP1
9.Peripheral Neuropathies and Charcot–Marie–Tooth Disease
Genes relevant to demyelinating and axonal neuropathies:
❖ GJB1, MFN2, SH3TC2, GDAP1, HSPB1, HSPB8, LITAF, PRX, NEFL, PMP22
10.Lysosomal Storage Disorders and Metabolic Neuropathies
Genes underlying defects in lysosomal degradation and metabolic pathways:
❖ GBA1, HEXA, SMPD1, MCOLN1, NPC1, NPC2, CYP7B1, GALC, GALT, PAH
11.Mitochondrial Fusion, Fission, and Dynamics
Genes controlling mitochondrial morphology and movement within neurons:
❖ MFN2, OPA1, OPA3, DNM2, KIF5A
12.Collagen, Vascular, and Small Vessel Disease Genes
Genes associated with cerebrovascular fragility and small vessel pathology:
❖ COL4A1, COL4A2, HTRA1, NOTCH3
13.Multisystem Disorders with Neurological Involvement
Genes contributing to systemic conditions with consistent neurological phenotypes:
❖ TSC1, TSC2, ATP7B,
Genes Analyzed 203 Neurology-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.Epilepsy and Seizure Disorders
❖ Identify monogenic epilepsies and developmental/epileptic encephalopathies
❖ Guide antiseizure medication selection and avoidance
❖ Stratify patients based on immune tolerance and toxicity risk
❖ Inform timing of interventions such as epilepsy surgery, neuromodulation, or ketogenic diet
❖ Support family counseling regarding recurrence risk and expected clinical course
2.Neuromuscular Disorders and Peripheral Neuropathies
❖ Detect hereditary myopathies, muscular dystrophies, congenital myasthenic syndromes, and Charcot–Marie–Tooth neuropathies
❖ Guide cardiac, respiratory, and orthopedic surveillance in neuromuscular disease
❖ Inform eligibility for gene-targeted or enzyme replacement therapies where available
3.Movement Disorders, Ataxias, and Neurodegenerative Syndromes
❖ Clarify the etiology of early-onset parkinsonism, dystonia, ataxia, and spastic paraplegia
❖ Differentiate neurodegenerative, metabolic, and structural causes with overlapping phenotypes
❖ Inform neuroprotective and rehabilitative strategies tailored to the underlying variant(s)
❖ Guide appropriate imaging, biomarker testing, and subspecialty referrals
4.Complex Neurological Presentations and Long-Term Management
❖ Provide molecular clarification in patients with mixed or nonspecific neurological features
❖ Support integrated care planning across neurology, genetics, rehabilitation, and psychiatry
❖ Facilitate updates to care as variant classifications and neurogenetic guidelines evolve
Precision Diagnosis
Identify the molecular cause of epilepsy, neuromuscular disease, hereditary neuropathy, leukodystrophy, or early-onset neurodegeneration when clinical features are overlapping or nonspecific.
Therapy Selection and Avoidance
Guide medication decisions—such as sodium channel blocker avoidance in SCN1A-related epilepsy or selection of targeted therapies for metabolic, mitochondrial, or treatable neurometabolic disorders.
Family Risk Assessment and Carrier Evaluation
Clarify recurrence risk in families, identify carriers, and support reproductive planning based on confirmed pathogenic variants.
Comprehensive Neurological Risk Management
Inform multidisciplinary care by integrating genetic, metabolic, and neurodegenerative risk factors into a unified clinical profile that supports long-term, personalized neurological management.
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.
Neurogenetic testing has become a central component of modern precision neurology, enabling clinicians to identify the molecular drivers of complex neurological disorders with far greater accuracy than traditional diagnostic approaches. With a carefully curated gene panel, high analytic performance, and clinically grounded interpretation, PreCheck Health Services equips providers with the genomic insights needed to guide diagnosis, optimize therapy, refine prognosis, and support long-term neurological management. This comprehensive approach empowers clinicians to deliver more precise, proactive, and personalized care across the full spectrum of neurological disease.
The Comprehensive Neurology Panel is designed to detect single-nucleotide variants (SNVs) and small insertions and deletions in 203 genes associated with neurological disorder/risk. 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.
AARS2, ABCD1, ACADM, ADCY5, AFG3L2, AIFM1, ALDH7A1, ANG, ANO10, ANXA11, APOE, APP, APTX, ARSA, ATL1, ATP13A2, ATP1A2, ATP1A3, ATP7B, BCKDHA, BCKDHB, BCS1L, BSCL2, C19ORF12, C21ORF2, CACNA1A, CAPN1, CDKL5, CHCHD10, CHD2, CHMP2B, COASY, COL4A1, COL4A2, COQ2, COQ8A, COX10, CP, CSF1R, CST3, CTSF, CYP7B1, DCTN1, DDHD1, DDHD2, DGUOK, DHCR7, DNA2, DNAJB2, DNAJC5, DNAJC6, DNM2, DNMT1, DYNC1H1, EGR2, ELP1, ERLIN2, FANCC, FBXO7, FGF14, FIG4, FTL, FUS, G6PC, GAA, GABRG2, GALC, GALT, GBA, GBE1, GCH1, GDAP1, GFAP, GJB1, GLA, GNAL, GNB4, GRID2, GRIN2A, GRN, GSN, HBB, HEPACAM, HEXA, HINT1, HNRNPA1, HNRNPA2B1, HSPB1, HSPB8, HTRA1, INF2, ITPR1, KCNA1, KCNC3, KCNQ2, KIF5A, LITAF, LMNB1, LRRK2, MAPT, MATR3, MCOLN1, MECP2, MFN2, MGME1, MME, MPV17, MPZ, NEFL, NEK1, NIPA1, NOTCH3, NPC1, NPC2, OPA1, OPA3, OPTN, PAH, PANK2, PARK7, PCDH19, PDGFB, PDSS2, PFN1, PINK1, PLA2G6, PLP1, PMP22, PNKD, PNPLA6, POLG, POLG2, PRKCG, PRKRA, PRNP, PRPS1, PRRT2, PRX, PSEN1, PSEN2, RAB39B, REEP1, RRM2B, SACS, SCN1A, SCN1B, SCN2A, SCN8A, SCO1, SCO2, SETX, SGCE, SH3TC2, SLC25A4, SLC2A1, SLC52A2, SLC52A3, SLC9A6, SMPD1, SNCA, SOD1, SORD, SPAST, SPG11, SPG7, SPTBN2, SPTLC1, SPTLC2, SQSTM1, SSBP1, STUB1, STXBP1, SUCLA2, SUCLG1, SYNGAP1, SYNJ1, TAFAZZIN, TARDBP, TBK1, TCF4, TH, THAP1, TK2, TOR1A, TPP1, TREM2, TREX1, TRPV4, TSC1, TSC2, TTBK2, TTR, TUBA4A, TWNK, TYMP, UBQLN2, VAPB, VCP, VPS35, WASHC5, WDR45, ZEB2, ZFYVE26
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 neurological pathology whose clinical association has not yet been definitively established. The test may therefore not detect all variants associated with neurological pathology. 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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