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  • Test code: 06230
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit
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Invitae Hyperammonemia Panel

Test description

The Invitae Hyperammonemia Panel analyzes genes that are associated with the enzymes and transporter proteins responsible for the production and detoxification of ammonia, the waste product of protein metabolism. Deficiency of any of these proteins may result in an excess of ammonia in the blood, hyperammonemia. If this condition is untreated it can cause severe brain damage and death. The genes in this panel were selected based on the available evidence to date and represent Invitae’s broadest test for disorders associated with hyperammonemia.

Please note that this panel includes genes associated with an increased risk for cancer (i.e. RINT1).

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Primary panel (76 genes)

ABCD4 ACADM ACADVL ALDH18A1 AMT ARG1 ASL ASS1 ATP5A1 ATP5D ATP5E ATPAF2 BCKDHA BCKDHB BTD CA5A CPS1 CPT1A CPT2 CYC1 DBT DLAT DLD ETFA ETFB ETFDH FBXL4 GLDC GLUD1 GLUL HADHA HADHB HCFC1 HLCS HMGCL IVD LMBRD1 LYRM7 MCCC1 MCCC2 MCEE MMAA MMAB MMACHC MMADHC MTR MTRR MUT NAGS NBAS NR1H4 OAT OTC PC PCCA PCCB PDHA1 PDHB PDHX PDP1 PRDX1 RINT1 SERAC1 SLC22A5 SLC25A13 SLC25A15 SLC25A20 SLC25A42 SLC7A7 TANGO2 TAZ TMEM70 TUFM UMPS UQCRC2 YARS2

  • Methylmalonic aciduria and homocystinuria due to cobalamin J (cblJ) deficiency
  • Medium chain acyl-CoA dehydrogenase deficiency
  • Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency
  • ALDH18A1-related conditions:
    • Delta-pyrroline-5-carboxylate synthetase (P5CS) deficiency
    • Cutis laxa (ADCL3 and ARCL3A)
    • Spastic paraplegia (SPG9A and SPG9B)
  • Glycine encephalopathy
  • Arginase deficiency
  • Argininosuccinate lyase deficiency
  • Citrullinemia type I
  • Combined oxidative phosphorylation deficiency 22, Mitochondrial complex V (ATP synthase) deficiency nuclear type 4, Schizophrenia
  • Mitochondrial complex V (ATP synthase) deficiency nuclear type 5
  • Mitochondrial complex V (ATP synthase) deficiency nuclear type 3
  • Mitochondrial complex V (ATP synthase) deficiency nuclear type 1
  • Maple syrup urine disease (MSUD)
  • Biotinidase deficiency
  • Carbonic anhydrase VA deficiency (CAVA)
  • Carbamoyl phosphate synthetase 1 (CPS1) deficiency
  • Carnitine palmitoyltransferase 1 (CPT1)
  • Carnitine palmitoyltransferase 2 (CPT2)
  • CYC1-related cytochrome-c-oxidase (COX) deficiency
  • Pyruvate dehydrogenase E2 (PDHE2) deficiency
  • Dihydrolipoamide dehydrogenase deficiency (DLD)
  • Multiple acyl-CoA dehydrogenase deficiency (MADD) (Glutaric acidemia type II)
  • Mitochondrial DNA depletion syndrome 13, encephalomyopathic type
  • Hyperinsulinism-hyperammonemia (HI/HA) syndrome
  • Glutamine synthetase deficiency
  • HADHA-related conditions
  • Mitochondrial trifunctional protein deficiency (MTP)
  • Cobalamin X (cblX) deficiency
  • Holocarboxylase synthetase deficiency
  • 3-hydroxy-3-methylglutaryl (HMG)-CoA lyase deficiency
  • Isovaleric acidemia
  • Methylmalonic aciduria with homocystinuria due to cobalamin F deficiency (MMAcblF)
  • Mitochondrial complex III deficiency, nuclear type 8
  • 3 Methylcrotonyl-CoA carboxylase deficiency (3MCC)
  • Methylmalonyl-CoA epimerase deficiency
  • Methylmalonic aciduria cobalamin A type (MMACblA)
  • Methylmalonic aciduria cobalamin B type (MMACblB)
  • Methylmalonic aciduria with homocystinuria due to cobalamin C (cblC) deficiency
  • Methylmalonic aciduria with homocystinuria due to cobalamin D (cblD) deficiency
  • Cobalamin G (cblG) deficiency
  • Cobalamin E (cblE) deficiency
  • Methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency
  • N-acetylglutamate synthase (NAGS) deficiency
  • Infantile liver failure syndrome, Short stature with optic nerve atrophy and Pelger-Huët anomaly (SOPH) syndrome
  • Progressive familial intrahepatic cholestasis (PFIC)
  • Gyrate atrophy of choroid and retina (GACR)
  • Ornithine transcarbamylase (OTC) deficiency
  • Pyruvate carboxylase deficiency
  • Propionic acidemia (PA)
  • Pyruvate dehydrogenase E1-alpha (PDHE1α) deficiency
  • Pyruvate dehydrogenase complex (PDHC) deficiency
  • Pyruvate dehydrogenase phosphatase deficiency (PDHPD)
  • Epi-cobalamin C (epi-cblC) deficiency
  • Infantile liver failure syndrome
  • 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like (MEGDEL) syndrome
  • Primary carnitine deficiency
  • Citrin deficiency
  • Hyperornithinemia-hyperammonemia-homocystinuria (HHH) syndrome
  • Carnitine-acylcarnitine translocase (CACT) deficiency
  • Mitochondrial myopathy
  • Lysinuric protein intolerance (LPI)
  • Recurrent metabolic crises with rhabdomyolysis, cardiac arrhythmias and neurodegeneration (MECRCN)
  • TAZ-related conditions:
    • Barth Syndrome (3-methylglutaconic aciduria type II)
    • Dilated cardiomyopathy (DCM)
    • Left ventricular noncompaction cardiomyopathy
  • ATP synthase deficiency
  • Combined oxidative phosphorylation deficiency 4 (COXPD4)
  • Orotic aciduria
  • Mitochondrial complex III deficiency, nuclear type 5
  • YARS2-related myopathy, lactic acidosis, and sideroblastic anemia (MLASA2)

To view the complete clinical description of this panel, click here.

Conditions associated with hyperammonemia follow a variety of inheritance patterns including autosomal recessive, autosomal dominant, and X-linked. Several conditions follow both autosomal recessive and autosomal dominant inheritance.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ABCD4 NM_005050.3
ACADM NM_000016.5
ACADVL NM_000018.3
ALDH18A1 NM_002860.3
AMT NM_000481.3
ARG1 NM_000045.3
ASL NM_000048.3
ASS1 NM_000050.4
ATP5A1 NM_001001937.1
ATP5D NM_001001975.1
ATP5E NM_006886.3
ATPAF2 NM_145691.3
BCKDHA NM_000709.3
BCKDHB NM_183050.2
BTD NM_000060.3
CA5A NM_001739.1
CPS1 NM_001875.4
CPT1A NM_001876.3
CPT2 NM_000098.2
CYC1 NM_001916.4
DBT NM_001918.3
DLAT NM_001931.4
DLD NM_000108.4
ETFA NM_000126.3
ETFB NM_001985.2
ETFDH NM_004453.3
FBXL4 NM_012160.4
GLDC NM_000170.2
GLUD1 NM_005271.4
GLUL NM_002065.6
HADHA NM_000182.4
HADHB NM_000183.2
HCFC1 NM_005334.2
HLCS NM_000411.6
HMGCL NM_000191.2
IVD NM_002225.3
LMBRD1 NM_018368.3
LYRM7 NM_181705.3
MCCC1 NM_020166.4
MCCC2 NM_022132.4
MCEE NM_032601.3
MMAA NM_172250.2
MMAB NM_052845.3
MMACHC NM_015506.2
MMADHC NM_015702.2
MTR NM_000254.2
MTRR* NM_002454.2
MUT NM_000255.3
NAGS NM_153006.2
NBAS NM_015909.3
NR1H4 NM_005123.3
OAT* NM_000274.3
OTC* NM_000531.5
PC* NM_000920.3
PCCA NM_000282.3
PCCB NM_000532.4
PDHA1 NM_000284.3
PDHB NM_000925.3
PDHX NM_003477.2
PDP1 NM_018444.3
PRDX1 NM_002574.3
RINT1 NM_021930.4
SERAC1 NM_032861.3
SLC22A5 NM_003060.3
SLC25A13 NM_014251.2
SLC25A15 NM_014252.3
SLC25A20 NM_000387.5
SLC25A42 NM_178526.4
SLC7A7 NM_001126106.2
TANGO2 NM_152906.6
TAZ NM_000116.4
TMEM70 NM_017866.5
TUFM NM_003321.4
UMPS NM_000373.3
UQCRC2 NM_003366.3
YARS2 NM_001040436.2

MTRR: Analysis includes the intronic variant NM_002454.2:c.903+469T>C.
OAT: Deletion/duplication analysis is not offered for exon 2.
OTC: Analysis includes the intronic variant NM_000531.5:c.540+265G>A.
PC: Analysis includes the intronic variant NM_000920.3:c.1369-29A>G.