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Overgrowth and Macrocephaly Syndromes Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
ABCC9 81479,81479
ADK 81479,81479
AKT1 81479,81479
AKT2 81479,81479
AKT3 81479,81479
ANKH 81479,81479
ASPA 81479,81479
ASXL2 81479,81479
BLTP1 81479,81479
BRSK2 81479,81479
BRWD3 81479,81479
CCND2 81479,81479
CDKN1C 81479,81479
CHD3 81479,81479
CHD4 81479,81479
CHD8 81479,81479
CUL4B 81479,81479
D2HGDH 81479,81479
DHCR24 81479,81479
DICER1 81479,81479
DIS3L2 81479,81479
DNMT3A 81479,81479
DVL1 81479,81479
EED 81479,81479
EIF2B5 81406,81479
ERF 81479,81479
ETFA 81479,81479
ETFB 81479,81479
ETFDH 81479,81479
EXT2 81479,81479
EZH2 81236,81479
FBLN5 81479,81479
FBN1 81408,81479
FGFR3 81479,81479
FOXP1 81479,81479
GATAD2B 81479,81479
GCDH 81406,81479
GFAP 81405,81479
GLI3 81479,81479
GPC3 81479,81479
GPC4 81479,81479
GPSM2 81479,81479
GRIA3 81479,81479
H1-4 81479,81479
H19 81479,81479
HEPACAM 81479,81479
HERC1 81479,81479
HRAS 81404,81479
HUWE1 81479,81479
KCNH1 81479,81479
KDM1A 81479,81479
KIF7 81479,81479
KMT2E 81479,81479
KPTN 81479,81479
KRAS 81405,81479
L1CAM 81407,81479
LAMB1 81479,81479
LBR 81479,81479
MED12 81479,81479
MITF 81479,81479
MLC1 81479,81479
MPDZ 81479,81479
MTM1 81405,81479
MTOR 81479,81479
NF1 81408,81479
NFIA 81479,81479
NFIB 81479,81479
NFIX 81479,81479
NONO 81479,81479
NPR2 81479,81479
NRAS 81479,81479
NSD1 81406,81405
ODC1 81479,81479
OFD1 81479,81479
PDGFRB 81479,81479
PHF21A 81479,81479
PHF6 81479,81479
PIGA 81479,81479
PIGM 81479,81479
PIK3CA 81479,81479
PIK3R2 81479,81479
PPP1CB 81479,81479
PPP2R5D 81479,81479
PTCH1 81479,81479
PTEN 81321,81323
RAB39B 81479,81479
RIN2 81479,81479
RNF125 81479,81479
RNF135 81479,81479
SETD2 81479,81479
SHANK3 81479,81479
SHOC2 81405,81479
SNX14 81479,81479
SOS1 81406,81479
SPRED1 81405,81479
STRADA 81479,81479
SUFU 81479,81479
SUZ12 81479,81479
SYN1 81479,81479
SZT2 81479,81479
TBC1D7 81479,81479
TCF20 81479,81479
TGFB3 81479,81479
TMEM94 81479,81479
TRIO 81479,81479
TRIP12 81479,81479
TSC1 81406,81405
TSC2 81407,81406
UPF3B 81479,81479
WNT5A 81479,81479
ZBTB20 81479,81479
ZBTB7A 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
3449Genes x (112)81479 81236(x1), 81321(x1), 81323(x1), 81404(x1), 81405(x7), 81406(x6), 81407(x2), 81408(x2), 81479(x203) $1290 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Eric Bend, PhD

Clinical Features and Genetics

Clinical Features

Overgrowth and macrocephaly syndromes constitute a heterogeneous group of developmental disorders that share growth excess as a predominant clinical feature. The majority of the disorders in this group are extremely rare. This panel is designed to aid the molecular diagnosis of disorders with features of macrocephaly (occipitofrontal circumference >98 percentile) and/or overgrowth that may be generalized, segmental, symmetric, or asymmetric. Excess growth can occur as an isolated feature or as part of a multiple malformation syndrome. Frequently, overgrowth disorders are associated with developmental delay, intellectual disability, and seizures, and may predispose patients to certain cancers (Olney et al. 2007. PubMed ID: 17980309; Verge and Mowat. 2010. PubMed ID: 20371592).

The physiological mechanisms of overgrowth are diverse, involving an increase in cell number, cell volume, or tissue proliferation. In many of the overgrowth disorders, these defects occur early in development resulting in prenatal or neonatal onset. However, in some conditions growth excess may not be appreciated until childhood. This panel targets over 40 disorders that include excess growth as a prominent and early symptom of the disease.

There are currently no treatments for constitutional overgrowth syndromes. However, molecular diagnosis can provide valuable prognostic information for guiding clinical management particularly related to cancer surveillance (Mester and Eng. 2013. PubMed ID: 23613428, Neylon et al. 2012 PubMed ID: 22705997).


The majority of overgrowth- and macrocephaly-related disorders are inherited in an autosomal dominant manner; however, recessive and X-linked inheritance is also observed. Many of the overgrowth syndromes are caused by activation (often loss of inhibition) of the PI3K/AKT/mTOR tyrosine receptor kinase pathway (AKT1, AKT2, AKT3, MTOR, PIK3CA, PIK3R2, PTEN, and TBC1D7), which plays a central role in cell growth and proliferation, angiogenesis, metabolism, and cell survival (Mester and Eng. 2013. PubMed ID: 23613428). Other molecular mechanisms involve the sonic hedgehog signaling pathway (GLI3, KIF7 and PTCH1) and cell cycle checkpoints (CCND2, CDKN1C, CUL4B, DIS3L2, HUWE1, OFD1, PPP2R5B, PPP2R5C, PPP2R5D, and STRADA) to name a few.

Due to the diverse functions of the genes involved, all varieties of pathogenic variants have been reported including, missense, nonsense, frameshift, gross deletions, and structural rearrangements (Human Genome Mutation Database). Pathogenic regulatory variants in the promoter of the PTEN gene have also been described. This test includes coverage of this clinically relevant region (from c.-700 to c.-1400). Among the conditions that are well characterized, penetrance is nearly 100%. For those that are dominant, de novo pathogenic variants are common. Finally, a subset of overgrowth conditions involve somatic mosaicism. This panel is not validated for detecting mosaic variants.

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

The analytical sensitivity of this test for detecting small sequence variation is >99%. The clinical sensitivity for making a positive diagnosis will vary considerably depending on the condition involved. It is expected to be very high for the well-characterized recognizable syndromes that are predominantly caused by small sequence variants. Examples from the literature include Sotos syndrome (~90%; Saugier-Veber et al. 2007. PubMed ID: 17565729) and Bannayan-Riley-Ruvalcaba syndrome (~70%; Marsh et al. 1998. PubMed ID: 9467011). Conditions with less defining features, such as Weaver syndrome, are expected to have lower diagnostic rates (~5%; Tatton-Brown et al. 2011. PubMed ID: 22190405). Finally, the sensitivity for Beckwith Wiedmann syndrome will be low (~5%), since this disorder is predominantly caused by methylation defects (Shuman et al. 2016. PubMed ID: 20301568).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides typically 99.2% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

This test is appropriate for individuals with clinical features that include macrocephaly (occipitofrontal circumference >98 percentile) or overgrowth that may be generalized, segmental, symmetric, or asymmetric. Importantly, this test is not validated for detecting mosaic variants with a low variant allele fraction, as expected in conditions such as Proteus syndrome (AKT1) and PIK3CA-related overgrowth syndromes (PIK3CA).


Official Gene Symbol OMIM ID
ABCC9 601439
ADK 102750
AKT1 164730
AKT2 164731
AKT3 611223
ANKH 605145
ASPA 608034
ASXL2 612991
BLTP1 611565
BRSK2 609236
BRWD3 300553
CCND2 123833
CDKN1C 600856
CHD3 602120
CHD4 603277
CHD8 610528
CUL4B 300304
D2HGDH 609186
DHCR24 606418
DICER1 606241
DIS3L2 614184
DNMT3A 602769
DVL1 601365
EED 605984
EIF2B5 603945
ERF 611888
ETFA 608053
ETFB 130410
ETFDH 231675
EXT2 608210
EZH2 601573
FBLN5 604580
FBN1 134797
FGFR3 134934
FOXP1 605515
GATAD2B 614998
GCDH 608801
GFAP 137780
GLI3 165240
GPC3 300037
GPC4 300168
GPSM2 609245
GRIA3 305915
H1-4 142220
H19 103280
HEPACAM 611642
HERC1 605109
HRAS 190020
HUWE1 300697
KCNH1 603305
KDM1A 609132
KIF7 611254
KMT2E 608444
KPTN 615620
KRAS 190070
L1CAM 308840
LAMB1 150240
LBR 600024
MED12 300188
MITF 156845
MLC1 605908
MPDZ 603785
MTM1 300415
MTOR 601231
NF1 613113
NFIA 600727
NFIB 600728
NFIX 164005
NONO 300084
NPR2 108961
NRAS 164790
NSD1 606681
ODC1 165640
OFD1 300170
PDGFRB 173410
PHF21A 608325
PHF6 300414
PIGA 311770
PIGM 610273
PIK3CA 171834
PIK3R2 603157
PPP1CB 600590
PPP2R5D 601646
PTCH1 601309
PTEN 601728
RAB39B 300774
RIN2 610222
RNF125 610432
RNF135 611358
SETD2 612778
SHANK3 606230
SHOC2 602775
SNX14 616105
SOS1 182530
SPRED1 609291
STRADA 608626
SUFU 607035
SUZ12 606245
SYN1 313440
SZT2 615463
TBC1D7 612655
TCF20 603107
TGFB3 190230
TMEM94 618163
TRIO 601893
TRIP12 604506
TSC1 605284
TSC2 191092
UPF3B 300298
WNT5A 164975
ZBTB20 606025
ZBTB7A 605878
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Achondroplasia AD 100800
Acrocallosal Syndrome, Schinzel Type AR 200990
Acromesomelic Dysplasia Maroteaux Type AR 602875
Acromicric Dysplasia AD 102370
Al-Gazali-Bakalinova syndrome AR 607131
Alexander Disease AD 203450
Alkuraya-Kucinskas syndrome AR 617822
Aml - Acute Myeloid Leukemia 601626
Arrhythmogenic Right Ventricular Cardiomyopathy, Type 1 AD 107970
Arteriovenous Malformations Of The Brain 108010
Autism, Susceptibility to, 18 AD 615032
Basal cell nevus syndrome 2 620343
Beckwith-Wiedemann Syndrome AD 130650
Bladder Cancer 109800
Borjeson-Forssman-Lehmann Syndrome XL 301900
Brain malformations with or without urinary tract defects AD 613735
Camptodactyly, Tall Stature, And Hearing Loss Syndrome AD 610474
Cardiofaciocutaneous syndrome 2 AD 615278
Cervical Cancer 603956
Charcot-Marie-Tooth disease, demyelinating, type 1H AD 619764
Chitayat Syndrome AD 617180
Chondrocalcinosis 2 AD 118600
Chudley-McCullough syndrome AR 604213
Cleft Palate, Psychomotor Retardation, and Distinctive Facial Features AD 616728
Cohen-Gibson syndrome AD 617561
COMMAD syndrome AR 617306
Corpus Callosum, Partial Agenesis Of, X-Linked XL 304100
Costello Syndrome AD 218040
Cowden Disease AD 158350
Cowden syndrome 5 AD 615108
Cowden syndrome 6 AD 615109
Craniometaphyseal Dysplasia, Autosomal Dominant AD 123000
Craniosynostosis 4 AD 600775
Crouzon Syndrome With Acanthosis Nigricans AD 612247
Cutis Laxa, Autosomal Dominant 2 AD 614434
Cutis Laxa, Autosomal Recessive, Type IA AR 219100
D-2-Alpha Hydroxyglutaric Aciduria AR 600721
Desmosterolosis AR 602398
Developmental delay with variable intellectual impairment and behavioral abnormalities AD 618430
Ectopia Lentis, Isolated, Autosomal Dominant AD 129600
Epidermal Nevus 162900
Epilepsy, X-Linked, With Variable Learning Disabilities And Behavior Disorders XL 300491
Epileptic encephalopathy, early infantile, 18 AR 615476
Epiphyseal chondrodysplasia, Miura type AD 615923
Exostoses, Multiple, Type II AD 133701
Familial Cancer Of Breast 114480
Familial Colorectal Cancer 114500
Fg Syndrome XL 305450
Focal Cortical Dysplasia Of Taylor 607341
Geleophysic Dysplasia 2 AD 614185
GLOW syndrome, somatic mosaic 618272
Glutaric Aciduria, Type 1 AR 231670
Glutaric Aciduria, Type 2 AR 231680
Glycosylphosphatidylinositol Deficiency AR 610293
Goiter, Multinodular 1, With Or Without Sertoli-Leydig Cell Tumors AD 138800
Gorlin Syndrome AD 109400
Greenberg Dysplasia AR 215140
Greig Cephalopolysyndactyly Syndrome AD 175700
Hereditary Diffuse Gastric Cancer 137215
Hereditary Gingival Fibromatosis AD 135300
Holoprosencephaly 7 AD 610828
Hydrocephalus, Nonsyndromic, Autosomal Recessive 2 AR 615219
Hypermethioninemia Due To Adenosine Kinase Deficiency AR 614300
Hyperphosphatasemia Tarda AR 239100
Hypertrichotic Osteochondrodysplasia AD 239850
Hypochondroplasia AD 146000
Hypoglycemia, Neonatal, Simulating Foetopathia Diabetica AD 240900
IMAGE Syndrome AD 614732
Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures AD 618725
Intellectual developmental disorder with cardiac defects and dysmorphic facies AR 618316
Intellectual developmental disorder, autosomal dominant 63, with macrocephaly AD 618825
Intellectual developmental disorder, X-linked 50 XL 300115
Joubert Syndrome 10 XL 300804
Joubert Syndrome 32 AR 617757
Juvenile Myelomonocytic Leukemia 607785
Keipert syndrome XL 301026
Kosaki overgrowth syndrome AD 616592
Lacrimoauriculodentodigital Syndrome AD 149730
Legius Syndrome AD 611431
Leukoencephalopathy with vanishing white matter 5, with or without ovarian failure AR 620315
Lissencephaly 5 AR 615191
Loeys-Dietz Syndrome 5 AD 615582
Lujan-Fryns Syndrome XL 309520
Lung Cancer 211980
Luscan-Lumish Syndrome AD 616831
Lymphangioleiomyomatosis 606690
Macrocephaly, acquired, with impaired intellectual development AD 618286
Macrocephaly, Alopecia, Cutis Laxa, And Scoliosis AR 613075
Macrocephaly, dysmorphic facies, and psychomotor retardation AR 617011
Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin AD 619769
Macrocephaly/Autism Syndrome AD 605309
Macrocephaly/megalencephaly syndrome, autosomal recessive AR 248000
Marfan lipodystrophy syndrome AD 616914
Marfan Syndrome AD 154700
Marshall-Smith Syndrome AD 602535
MASA Syndrome XL 303350
Mass Syndrome AD 604308
Medulloblastoma AR 155255
Megalencephalic Leukoencephalopathy With Subcortical Cysts AR 604004
Megalencephalic Leukoencephalopathy With Subcortical Cysts 2A AR 613925
Megalencephalic Leukoencephalopathy With Subcortical Cysts 2B, Remitting, With Or Without Mental Retardation AD 613926
Megalencephaly-Capillary Malformation-Polymicrogyria syndrome, Somatic 602501
Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1 AD 603387
Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 2 AD 615937
Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 3 AD 615938
Melanoma, cutaneous malignant, susceptibility to, 8 614456
Meningioma, Familial AD 607174
Mental Retardation With Language Impairment And Autistic Features AD 613670
Mental Retardation, Autosomal Dominant 18 AD 615074
Mental retardation, autosomal dominant 35 AD 616355
Mental Retardation, Autosomal Dominant 44 AD 617061
Mental Retardation, Autosomal Dominant 49 AD 617752
Mental retardation, autosomal recessive 41 AR 615637
Mental Retardation, X-Linked 72 XL 300271
Mental Retardation, X-Linked 93 XL 300659
Mental retardation, X-linked syndromic, Turner type XL 309590
Mental Retardation, X-Linked, Syndromic 14 XL 300676
Mental Retardation, X-linked, Syndromic 34 XL 300967
Mental Retardation, X-Linked, Syndromic, Wu Type XL 300699
Mental Retardation, X-Linked, With Short Stature, Hypogonadism, And Abnormal Gait XL 300354
Muenke Syndrome AD 602849
Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 XL 300868
Neurocutaneous melanosis, somatic 249400
Neurodevelopmental disorder with alopecia and brain abnormalities AD 619075
Neurodevelopmental disorder with epilepsy and hemochromatosis 301072
Neurofibromatosis, Familial Spinal AD 162210
Neurofibromatosis, Type 1 AD 162200
Neurofibromatosis-Noonan Syndrome AD 601321
Neuropathy, Hereditary, with or without Age-Related Macular Degeneration AD 608895
Noonan Syndrome 3 AD 609942
Noonan Syndrome 4 AD 610733
Noonan Syndrome 6 AD 613224
Noonan syndrome-like disorder with loose anagen hair 2 AD 617506
Noonan-Like Syndrome With Loose Anagen Hair AD 607721
O'Donnell-Luria-Rodan syndrome AD 618512
Oculoectodermal syndrome, somatic 600268
OHDO Syndrome, X-linked; OHDOX XL 300895
Oral-Facial-Digital Syndrome XL 311200
Pallister-Hall Syndrome AD 146510
Pancreatic Cancer 260350
Paroxysmal Nocturnal Hemoglobinuria 300818
Pelger-Huet Anomaly AD 169400
Pelger-Huet anomaly with mild skeletal anomalies 618019
Perlman Syndrome AR 267000
Phelan-Mcdermid Syndrome AD 606232
Pleuropulmonary Blastoma AD 601200
Polydactyly Preaxial Type 4 AD 174700
Polydactyly, Postaxial, Type A1 AD 174200
Polyhydramnios, Megalencephaly, And Symptomatic Epilepsy AR 611087
Premature aging syndrome, Penttinen type AD 601812
Primrose Syndrome AD 259050
Rahman syndrome AD 617537
RAS-Associated Autoimmune Leukoproliferative Disorder 614470
Reynolds Syndrome AD 613471
Rhabdomyosarcoma, embryonal, 2 180295
Robinow Syndrome AD 180700
Robinow syndrome, autosomal dominant 2 AD 616331
SADDAN AD 616482
Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic 163200
Schizophrenia 15 AD 613950
Seizures, scoliosis, and macrocephaly syndrome AR 616682
Shashi-Pena syndrome AD 617190
Sifrim-Hitz-Weiss Syndrome AD 617159
Simpson-Golabi-Behmel Syndrome XL 312870
Simpson-Golabi-Behmel Syndrome, Type 2 XL 300209
Smith-Kingsmore Syndrome AD 616638
Snijders Blok-Campeau syndrome AD 618205
Sotos Syndrome 2 AD 614753
Sotos' Syndrome AD 117550
Spinocerebellar Ataxia, Autosomal Recessive 20 AR 616354
Spitz nevus or nevus spilus, somatic 137550
Spongy Degeneration Of Central Nervous System AR 271900
Stiff Skin Syndrome AD 184900
Tatton-Brown-Rahman Syndrome AD 615879
Temple-Baraitser Syndrome AD 611816
Tenorio Syndrome AD 616260
Testicular Cancer 273300
Thanatophoric Dysplasia Type 1 AD 187600
Thanatophoric Dysplasia Type 2 AD 187601
Thyroid Cancer, Follicular 188470
Tietz Syndrome AD 103500
Tuberous Sclerosis 1 AD 191100
Tuberous Sclerosis 2 AD 613254
Vacterl Association With Hydrocephalus AR 276950
Waardenburg Syndrome, Type 2A AD 193510
Waisman Syndrome XL 311510
Watson Syndrome AD 193520
Weaver Syndrome AD 277590
Weill-Marchesani Syndrome 2 AD 608328
X-Linked Hydrocephalus Syndrome XL 307000
Zimmermann-Laband Syndrome 1 AD 135500

Related Test



  • Human Gene Mutation Database (Biobase).
  • Marsh et al. 1998. PubMed ID: 9467011
  • Mester and Eng. 2013. PubMed ID: 23613428
  • Neylon et al. 2012. PubMed ID: 22705997
  • Olney. 2007. PubMed ID: 17980309
  • Saugier-Veber et al. 2007. PubMed ID: 17565729
  • Shuman et al. 2016. PubMed ID: 20301568
  • Tatton-Brown et al. 2011. PubMed ID: 22190405
  • Verge and Mowat. 2010. PubMed ID: 20371592


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

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PGxome (Exome) Sequencing Panel

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