4978 Santa Anita Ave Temple City, CA 91780 (p) 626-350-0537 (f) 626-454-1667 [email protected] www.fulgentgenetics.com Patient Information Partner Information Physician: Laboratory: Patient Last, Patient First Not Tested Physician Last, Physician First Fulgent Genetics DOB: Jan 01, 1900 ATTN: Physician Last, Physician First CAP#: 8042697 Sex: ? Portal Example Lab CLIA#: 05D2043189 MR#: 000-000-000 4978 Santa Anita Ave Laboratory Director: FD Patient#: FT-PT21496 Temple City, CA 91780 US Dr. Hanlin (Harry) Gao Phone: 626-350-0537 Report Date: Important Date Fax: 626-574-9669 Accession: Accession: FT-1612508 N/A Test#: FT-TS103644 Specimen Type: TBD Collection Date: DRAFT RESULTS TEST PERFORMED Sonic Beacon Female Carrier Carrier for ONE genetic condition. Screening Genetic counseling is recommended. (402 Gene Panel; gene sequencing with deletion and duplication analysis) Condition and Gene Inheritance Patient Last, Patient First Partner Fragile X syndrome X-linked Premutation carrier N/A FMR1 (29 repeats and 75 repeats; 2 AGG interruption detected) INTERPRETATION: Notes and Recommendations: Based on these results, there is increased risk to have a child with an FMR1-related condition. See below for details. Testing for copy number changes in the SMN1 gene was performed to screen for your carrier status for Spinal Muscular Atrophy. Two copies of the SMN1 gene were detected. These results are within the normal range for non-carriers. See Limitations section for more information. This carrier screening test does not screen for all possible genetic conditions, nor for all possible mutations in every gene tested. Individuals with negative test results may still have up to a 3-4% risk to have a child with a birth defect due to genetic and/or environmental factors. Patients may wish to discuss any carrier results with blood relatives, as there is an increased chance that they are also carriers. Patient: Patient Last, Patient First; Sex: ?; Accession#: FT-1612508; FD Patient#: FT-PT21496; DOB: Jan 01, 1900; MR#: 000-000-000 DocID: ; Page 1 of 21 4978 Santa Anita Ave Temple City, CA 91780 (p) 626-350-0537 (f) 626-454-1667 [email protected] www.fulgentgenetics.com Fragile X syndrome Patient Patient Last, Patient First Partner Result Premutation carrier N/A FMR1 repeat expansion Variant Details N/A 29 repeats and 75 repeats; 2 AGG interruption detected What is Fragile X syndrome? Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability worldwide. FXS syndrome typically causes moderate intellectual disability in males, although the severity of intellectual impairment varies from person to person. Some females affected with fragile X syndrome can have mild intellectual disability. Abilities range from mild learning disabilities to severe mental retardation. Behavioral characteristics include autism, hyperactivity, short attention span and poor eye contact. Carriers of a premutation are at risk for fragile X-associated tremor/ataxia syndrome (FXTAS) and premature ovarian failure (POF). FXTAS is a neurodegenerative disorder characterized by adult onset of intention tremor, gait ataxia, memory deficits, and cognitive deficits. What is my risk of having an affected child? Based on these results, male offspring have a 50% chance of inheriting this allele and being at risk for FXTAS. Female offspring have a 50% chance to be a carrier of this premutation. Additionally, there is up to a 64% chance of this repeat expanding to a full mutation in the next generation (PubMed: 25110527). If expansion were to occur in a female offspring, it would confer risk to have premature ovarian failure. If expansion were to occur in a male offspring, it could cause Fragile X syndrome. What kind of medical management is available? Children with Fragile X syndrome may benefit from educational support like early developmental intervention, special education classes in school, speech therapy, occupational therapy, and behavioral therapies. A small number may experience seizures, but in general, there are no severe medical issues and affected children have a normal life span. What mutation was detected? The mutation detected is a premutation repeat expansion allele of 75 repeats with two AGG interruptions. Patient: Patient Last, Patient First; Sex: ?; Accession#: FT-1612508; FD Patient#: FT-PT21496; DOB: Jan 01, 1900; MR#: 000-000-000 DocID: ; Page 2 of 21 4978 Santa Anita Ave Temple City, CA 91780 (p) 626-350-0537 (f) 626-454-1667 [email protected] www.fulgentgenetics.com GENES TESTED: Sonic Beacon Female Carrier Screening 402 genes tested (99.43% of coding bases at >20x). For more gene specific information and assistance with residual risk calculation, see SUPPLEMENTAL TABLE. ABCB11, ABCC8, ABCD1, ABCD4, ACAD9, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACOX1, ACSF3, ADA, ADAMTS2, ADGRG1, ADK, AGA, AGL, AGPS, AGXT, AHCY, AHI1, AIPL1, AIRE, ALDH3A2, ALDH4A1, ALDOB, ALG6, ALMS1, ALPL, AMT, AP1S2, AQP2, ARG1, ARL13B, ARSA, ARSB, ARSE, ARX, ASL, ASNS, ASPA, ASS1, ATM, ATP6V1B1, ATP7A, ATP7B, ATRX, BBS1, BBS10, BBS12, BBS2, BCKDHA, BCKDHB, BCS1L, BLM, BRWD3, BSND, BTD, CAPN3, CASQ2, CBS, CCDC103, CCDC151, CCDC39, CD40LG, CDH23, CEP290, CERKL, CFTR, CHM, CHRNE, CHRNG, CHST6, CIITA, CLN3, CLN5, CLN6, CLN8, CLRN1, CNGA1, CNGB1, CNGB3, COL27A1, COL4A3, COL4A4, COL4A5, COL7A1, CPS1, CPT1A, CPT2, CRB1, CRYL1, CTNS, CTSK, CUL4B, CYBA, CYBB, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP1B1, CYP21A2, CYP27A1, DBT, DCLRE1C, DCX, DHCR7, DHDDS, DLD, DLG3, DMD, DNAH5, DNAI1, DNAI2, DNAL1, DPYD, DUOX2, DUOXA2, DYSF, EDA, EIF2AK3, EIF2B5, ELP1, EMD, ERCC6, ERCC8, ESCO2, ETFA, ETFB, ETFDH, ETHE1, EVC, EVC2, EXOSC3, EYS, F11, F8, F9, FAH, FAM161A, FANCA, FANCC, FANCG, FGD1, FH, FKRP, FKTN, FMR1, FTCD, FTSJ1, G6PC, GAA, GALC, GALE, GALK1, GALNS, GALT, GAMT, GBA, GBE1, GCDH, GDAP1, GFM1, GJB1, GJB2, GJB6, GLA, GLB1, GLDC, GLE1, GNE, GNPTAB, GNPTG, GNRHR, GNS, GP1BA, GP9, GPR143, GRHPR, GUSB, HADHA, HAX1, HBA1, HBA2, HBB, HEXA, HEXB, HGD, HGSNAT, HJV, HLCS, HMGCL, HOGA1, HPS1, HPS3, HSD17B4, HSD3B2, HYAL1, HYLS1, IDH3B, IDS, IDUA, IL1RAPL1, IL2RG, IVD, IYD, JAK3, KCNJ11, KDM5C, L1CAM, LAMA2, LAMA3, LAMB3, LAMC2, LCA5, LHX3, LIFR, LIPA, LMBRD1, LOXHD1, LPL, LRPPRC, LYST, MAN2B1, MCCC1, MCCC2, MCEE, MCOLN1, MED17, MESP2, MFSD8, MKS1, MLC1, MMAA, MMAB, MMACHC, MMADHC, MPI, MPL, MPV17, MTM1, MTMR2, MTRR, MTTP, MUT, MVK, MYO7A, NAGLU, NAGS, NBN, NDP, NDRG1, NDUFAF5, NDUFS6, NEB, NPC1, NPC2, NPHP1, NPHS1, NPHS2, NR0B1, NR2E3, NTRK1, OAT, OCRL, OPA3, OPHN1, OTC, OTOF, P3H1, PAH, PAK3, PANK2, PC, PCBD1, PCCA, PCCB, PCDH15, PDE6A, PDHA1, PDHB, PEX1, PEX10, PEX12, PEX2, PEX6, PEX7, PFKM, PGK1, PHF8, PHGDH, PKHD1, PLA2G6, PLOD1, PMM2, POLG, POLR1C, POMGNT1, POMT1, POMT2, POU3F4, PPT1, PQBP1, PROP1, PRPS1, PSAP, PTS, PUS1, PYGM, QDPR, RAB23, RAG1, RAG2, RAPSN, RARS2, RAX, RDH12, RMRP, RP2, RPE65, RPGR, RPGRIP1L, RS1, RTEL1, SACS, SAMHD1, SEPSECS, SERPINA1, SGCA, SGCB, SGCD, SGCG, SGSH, SH3TC2, SLC12A3, SLC12A6, SLC16A2, SLC17A5, SLC22A5, SLC25A13, SLC25A15, SLC25A20, SLC26A2, SLC26A3, SLC26A4, SLC35A3, SLC37A4, SLC39A4, SLC46A1, SLC4A11, SLC5A5, SLC6A19, SLC6A8, SLC7A7, SMARCAL1, SMN1, SMPD1, SPG11, SPG7, STAR, SUMF1, SURF1, SYN1, TAT, TCIRG1, TECPR2, TFR2, TG, TGM1, TH, THOC2, TMEM216, TPO, TPP1, TRDN, TRIM32, TRMU, TSFM, TSHB, TTC37, TTPA, TYMP, UGT1A1, UPF3B, USH1C, USH1G, USH2A, VPS13A, VPS13B, VPS45, VRK1, VSX2, WAS, WHRN, WNT10A, XPA, XPC, ZDHHC9, ZFYVE26, ZNF711 METHODS: Genomic DNA was isolated from the submitted specimen indicated above (if cellular material was submitted). DNA was barcoded, and enriched for the coding exons of targeted genes using hybrid capture technology. Prepared DNA libraries were then sequenced using a Next Generation Sequencing technology. Following alignment to the human genome reference sequence (assembly GRCh37 / hg19), variants were detected in regions of at least 10x coverage. For this specimen, 99.49% and 99.43% of coding regions and splicing junctions of genes listed had been sequenced with coverage of at least 10x and 20x respectively or by Sanger sequencing. The remaining regions did not have 10x coverage, and were not evaluated. Variants were interpreted manually using locus specific databases, literature searches, and other molecular biological principles. All the variants with quality score less than 500 (roughly 40x of coverage for a heterozygous variant) will be confirmed by Sanger sequencing. Only variants classified as pathogenic, likely-pathogenic are reported. All genes listed were evaluated for large deletions and/or duplications. However, single exon deletions or duplications will not be detected in this assay, nor will copy number alterations in regions of genes with significant pseudogenes (see Gene Specific Limitations below). Putative deletions or duplications identified are confirmed by an orthogonal method (qPCR or MLPA). If included in the panel, FMR1 repeat analysis is performed by repeat-primed PCR (rpPCR) and amplicon length analysis. Methylation studies are not performed. Variants are classified using the ACMG Guidelines for Sequence Variant Interpretation (PubMed: 27993330) unless otherwise specified. Patient: Patient Last, Patient First; Sex: ?; Accession#: FT-1612508; FD Patient#: FT-PT21496; DOB: Jan 01, 1900; MR#: 000-000-000 DocID: ; Page 3 of 21 4978 Santa Anita Ave Temple City, CA 91780 (p) 626-350-0537 (f) 626-454-1667 [email protected] www.fulgentgenetics.com LIMITATIONS: General Limitations These test results and variant interpretation are based on the proper identification