Epilepsy Comprehensive NGS Panel

Panel Description

Diseases Targeted:

Encephalopathy

Epilepsy

Seizures

Spasms

Overview:

Epilepsy is a neurological condition characterized by recurrent seizures. The condition can be caused by injuries, illnesses, genetic factors, or in some cases, it can occur with no known cause. Epilepsy is typically diagnosed after a person has two or more unprovoked seizures. Symptoms of seizures vary, but some warning signs include jerky and uncontrollable movements in the arms and legs, loss of consciousness, confusion, sudden stiff muscles, and unprovoked feelings of fear or anxiety.

This panel is designed to include a comprehensive set of genes that have seizure activity as a possible clinical presentation in either syndromic or non-syndromic disease. All genes present in the Neonatal, Childhood, Adolescent/Adult, and PME Epilepsy Panels are included in this panel.

Who is this test for?

This panel is recommended for anyone with a personal and/or family history of epilepsy and seizures. Testing may be considered after a patient is diagnosed with epilepsy.

What are the potential benefits for my patient?

Genetic testing can help to establish or confirm a diagnosis of inherited epilepsy and identify the pathogenetic variant responsible. This can help guide treatment to manage and prevent additional seizures or other related health problems.

Genetic testing for epilepsy can:

Establish or confirm the appropriate diagnosis
Inform family members about their own risk factors
Identify risks for additional related symptoms
Result in more personalized treatment and symptom management
Provide information about clinical course of disease
Connect patients to relevant resources and support
Provide options for family planning

Test Description

Order Options:

Sequencing
Del/Dup
Rush / STAT
Exclude VUS
MCC
Duo/Trio

Turnaround Time:

3-5 weeks

Cost:

Call for details

Genes:

ABAT, ABCC8, ACY1, ADAR, ADGRG1, ADGRV1, ADRA2B, ADSL, AGA, AHI1, AKT3, ALDH4A1, ALDH5A1, ALDH7A1, ALG1, ALG12, ALG13, ALG2, ALG3, ALG6, ALG8, ALG9, AMACR, AMT, ANK3, ARFGEF2, ARG1, ARHGEF15, ARHGEF9, ARL13B, ARSA, ARSB, ARX, ASAH1, ASNS, ASPA, ASPM, ATIC, ATP13A2, ATP1A2, ATP2A2, ATP6AP2, ATP6V0A2, ATP7A, ATPAF2, ATRX, AUH, B4GALT1, BCKDK, BCS1L, BOLA3, BRAF, BRAT1, BRD2, BTD, BUB1B, C12orf57, CACNA1A, CACNA1H, CACNA2D2, CACNB4, CASK, CASR, CBL, CC2D2A, CCDC88C, CCL2, CDKL5, CENPJ, CEP290, CHD2, CHRNA2, CHRNA4, CHRNB2, CLCN2, CLCN4, CLN3, CLN5, CLN6, CLN8, CNTN2, CNTNAP2, COG7, COG8, COL18A1, COL4A1, COQ2, COQ8A, COQ9, COX10, COX15, CPA6, CPT2, CRH, CSTB, CTSA, CTSD, CTSF, CUL4B, CYFIP2, DCX, DEPDC5, DHCR7, DHFR, DLD, DNAJC5, DNM1, DOCK7, DOLK, DPAGT1, DPM1, DPM2, DPYD, DYNC1H1, DYRK1A, EEF1A2, EFHC1, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EMX2, EPM2A, ETFDH, FARS2, FASN, FGD1, FGFR3, FH, FKRP, FKTN, FLNA, FOLR1, FOXG1, FUCA1, GABRA1, GABRB2, GABRB3, GABRD, GABRG2, GALC, GAMT, GATM, GCDH, GCSH, GFAP, GLB1, GLDC, GLI2, GLI3, GLRA1, GLRB, GLUD1, GNAO1, GNE, GNS, GOSR2, GPC3, GPHN, GRIA3, GRIN1, GRIN2A, GRIN2B, GRN, HCN1, HCN4, HDAC4, HECW2, HEXA, HEXB, HGSNAT, HNRNPU, HPD, HRAS, HSD17B10, IDS, IQSEC2, IRF2BPL, KANSL1, KCNA1, KCNA2, KCNAB2, KCNB1, KCNC1, KCNC2, KCNH2, KCNJ10, KCNJ11, KCNMA1, KCNQ2, KCNQ3, KCNT1, KCNV2, KCTD7, KDM5C, KDM6A, KIF1BP, KMT2D, KPNA7, KRAS, L2HGDH, LAMA2, LARGE1, LBR, LGI1, LIAS, LRPPRC, MAP2K1, MAP2K2, MAPK10, MBD5, MCOLN1, MCPH1, MDH2, ME2, MECP2, MED12, MED17, MEF2C, MFSD8, MGAT2, MLC1, MOCS1, MOCS2, MOGS, MPDU1, MTHFR, MTOR, NAGLU, NDE1, NDUFA1, NDUFA2, NDUFS1, NDUFS3, NDUFS4, NDUFS7, NDUFS8, NDUFV1, NEDD4L, NEU1, NEXMIF, NF1, NGLY1, NHLRC1, NIPBL, NOTCH3, NPC1, NPC2, NPHP1, NPRL2, NPRL3, NR2F1, NRXN1, NSD1, NTNG1, OFD1, OPHN1, PAFAH1B1, PAK3, PANK2, PC, PCDH19, PCNT, PDHA1, PDSS2, PEX1, PEX12, PEX14, PEX2, PEX26, PEX3, PEX5, PEX6, PEX7, PGK1, PHF6, PIGA, PIGO, PIGV, PLA2G6, PLCB1, PLP1, PLPBP, PMM2, PNKP, PNPO, POLG, POMGNT1, POMT1, POMT2, PPP3CA, PPT1, PQBP1, PRICKLE1, PRICKLE2, PRODH, PRRT2, PSAP, PTCH1, PTPN11, PURA, QARS, QDPR, RAB39B, RAB3GAP1, RAI1, RARS2, RBFOX1, RBFOX3, RELN, RFT1, RNASEH2A, RNASEH2B, RNASEH2C, ROGDI, RPGRIP1L, RYR3, SAMHD1, SCARB2, SCN10A, SCN1A, SCN1B, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A, SCO2, SDHA, SERPINI1, SETBP1, SGSH, SHH, SHOC2, SIK1, SIX3, SLC12A5, SLC13A5, SLC17A5, SLC19A3, SLC1A3, SLC25A12, SLC25A15, SLC25A19, SLC25A22, SLC2A1, SLC35A1, SLC35A2, SLC35C1, SLC46A1, SLC4A10, SLC6A1, SLC6A8, SLC9A6, SMARCA2, SMC1A, SMC3, SMS, SNAP25, SPRED1, SPTAN1, SRGAP2, ST3GAL3, ST3GAL5, STIL, STX1B, STXBP1, SUMF1, SUOX, SURF1, SYN1, SYNGAP1, SYP, SZT2, TACO1, TBC1D24, TBL1XR1, TBX1, TCF4, TMEM67, TMEM70, TNK2, TPP1, TREX1, TSC1, TSC2, TSEN2, TSEN34, TSEN54, TUBA1A, TUBA8, TUBB2A, TUBB2B, TWNK, UBE2A, UBE3A, UNC80, VPS13A, VPS13B, WDR45, WWOX, ZEB2, ZIC2 ( 405 genes )

Coverage:

96% at 20x

Specimen Requirements:

Blood (two 4ml EDTA tubes, lavender top) or Extracted DNA (3ug in EB buffer) or Buccal Swab or Saliva (kits available upon request)

Test Limitations:

All sequencing technologies have limitations. This analysis is performed by Next Generation Sequencing (NGS) and is designed to examine coding regions and splicing junctions. Although next generation sequencing technologies and our bioinformatics analysis significantly reduce the contribution of pseudogene sequences or other highly-homologous sequences, these may still occasionally interfere with the technical ability of the assay to identify pathogenic variant alleles in both sequencing and deletion/duplication analyses. Sanger sequencing is used to confirm variants with low quality scores and to meet coverage standards. If ordered, deletion/duplication analysis can identify alterations of genomic regions which include one whole gene (buccal swab specimens and whole blood specimens) and are two or more contiguous exons in size (whole blood specimens only); single exon deletions or duplications may occasionally be identified, but are not routinely detected by this test. Identified putative deletions or duplications are confirmed by an orthogonal method (qPCR or MLPA). This assay will not detect certain types of genomic alterations which may cause disease such as, but not limited to, translocations or inversions, repeat expansions (eg. trinucleotides or hexanucleotides), alterations in most regulatory regions (promoter regions) or deep intronic regions (greater than 20bp from an exon). This assay is not designed or validated for the detection of somatic mosaicism or somatic mutations.

Gene Specifics:

Gene	Notes
MECP2	Currently available technologies (NGS and qPCR) are not amenable to detection of single exon deletions/duplications of exon 1 in the MECP2 gene.
MTHFR	As recommended by ACMG, the two common polymorphisms in the MTHFR gene - c.1286A>C (p.Glu429Ala, also known as c.1298A>C) and c.665C>T (p.Ala222Val, also known as c.677C>T) - are not reported in this test due to lack of sufficient clinical utility to merit testing (PubMed: 23288205).
ZIC2	The current testing method does not assess trinucleotide repeat expansions in this gene.

CPT Codes:

CPT Code

81403, 81404, 81405, 81406, 81407

NOTE: The CPT codes listed on the website are in accordance with Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided here for the convenience of our clients. Clients who bill for services should make the final decision on which codes to use.

Resources

Description	Download
Epilepsy Fact Sheet for Patients