Aorta Panel

Summary
Is a 53 gene panel that includes assessment of non-coding variants.

Is ideal for patients who have isolated or syndromic aortic disease presenting with ascending aortic dilatation, aneurysm or dissection.

Analysis methods
  • PLUS
Availability
4 weeks
Number of genes
53
Test code
CA1001
Panel tier
Tier 2
CPT Code *
81410(1), 81411(1)
* The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Summary

The Blueprint Genetics Aorta Panel (test code CA1001):

Read about our accreditations, certifications and CE-marked IVD medical devices here.

ICD Codes

Refer to the most current version of ICD-10-CM manual for a complete list of ICD-10 codes.

Sample Requirements

  • Blood (min. 1ml) in an EDTA tube
  • Extracted DNA, min. 2 μg in TE buffer or equivalent
  • Saliva (Please see Sample Requirements for accepted saliva kits)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

We do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue. In addition, if the patient is affected with a hematological malignancy, DNA extracted from a non-hematological source (e.g. skin fibroblasts) is strongly recommended.

Please note that, in rare cases, mitochondrial genome (mtDNA) variants may not be detectable in blood or saliva in which case DNA extracted from post-mitotic tissue such as skeletal muscle may be a better option.

Read more about our sample requirements here.

Aortic dilatation is defined by a diameter larger than 110% of reference value determined by age, sex, and body surface area. Progressing aortic dilatation eventually fulfills the definition of aortic aneurysm, which is a local aortic diameter higher than 150% of reference value. Usually aortic aneurysm formation is driven by reduced elastin content and fragmentation with concomitant smooth muscle cell loss, a process called cystic medial degeneration. Although this process is seen normally as a consequence of aging, it is accelerated in aortic aneurysm diseases. Most aortic aneurysms are associated with non-syndromic dilatation. However, at least 20% of aortic aneurysms are in the context of syndromic diseases such as Marfan syndrome (MfS), Loeys-Dietz syndrome (LDS), Shprintzen-Goldberg syndrome (SGS) and Ehlers-Danlos syndromes (EDS). Individuals with aortic aneurysms are at risk of sudden cardiac death due to rupture and dissection.

Genes in the Aorta Panel and their clinical significance

To view complete table content, scroll horizontally.

GeneAssociated phenotypesInheritanceClinVarHGMD
ABCC6*Pseudoxanthoma elasticumAR352377
ABL1Congenital heart defects and skeletal malformations syndrome (CHDSKM)AD305
ACTA2Aortic aneurysm, familial thoracic, Moyamoya disease, Multisystemic smooth muscle dysfunction syndromeAD2076
ADAMTS10Weill-Marchesani syndromeAR814
ADAMTS17Weill-Marchesani-like syndromeAR67
ADAMTS2#Ehlers-Danlos syndromeAR811
ADAMTSL4Ectopia lentis, isolatedAR1127
ALDH18A1Spastic paraplegia, Cutis laxaAD/AR2230
ATP7AMenkes disease, Occipital horn syndrome, Spinal muscular atrophy, distal, X-linked 3XL116354
B3GAT3#*Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defectsAR613
BGNSpondyloepimetaphyseal dysplasia, X-linked, Meester-Loeys syndromeXL87
CBSHomocystinuria due to cystathionine beta-synthase deficiencyAR88205
COL1A1Ehlers-Danlos syndrome, Caffey disease, Osteogenesis imperfecta type 1, Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4AD352962
COL1A2Ehlers-Danlos syndrome, cardiac valvular form, Osteogenesis imperfecta type 1, Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4AD/AR186509
COL2A1Avascular necrosis of femoral head, Rhegmatogenous retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasia, Achondrogenesis type 2, Platyspondylic dysplasia Torrance type, Hypochondrogenesis, Spondyloepiphyseal dysplasia congenital (SEDC), Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, Kniest dysplasia, Spondyloperipheral dysplasia, Mild SED with premature onset arthrosis, SED with metatarsal shortening, Stickler syndrome type 1AD/AR180561
COL3A1Ehlers-Danlos syndromeAD520631
COL4A5Alport syndrome, X-linkedXL704992
COL5A1Ehlers-Danlos syndromeAD101154
COL5A2Ehlers-Danlos syndromeAD2435
COLGALT1Brain small vessel diseaseAR
EFEMP2Cutis laxaAR1416
ELNCutis laxa, Supravalvular aortic stenosisAD78113
ENPP1Arterial calcification, Hypophosphatemic ricketsAD/AR2272
FBLN5Cutis laxa, Macular degeneration, age-relatedAD/AR1322
FBN1MASS syndrome, Marfan syndrome, Acromicric dysplasia, Geleophysic dysplasia 2AD14652679
FBN2Congenital contractural arachnodactyly (Beals syndrome)AD5097
FKBP14Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing lossAR56
FLNAFrontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects, Periventricular nodular heterotopia 1, Melnick-Needles syndrome, Intestinal pseudoobstruction, neuronal, X-linked/Congenital short bowel syndrome, Cardiac valvular dysplasia, X-linkedXL133257
FOXE3Aphakia, congenital primary, Anterior segment mesenchymal dysgenesis, Cataract 34, Aortic aneurysm, familial thoracicAR/AD929
GATA5Familial atrial fibrillation, Tetralogy of Fallot, Single ventricular septal defectAD532
HCN4Sick sinus syndrome, Brugada syndrome, Left ventricular non-compaction cardiomyopathy (LVNC)AD834
LOXAortic aneurysm, familial thoracic 10AD67
MAT2A*Complement systemAD/AR2
MED12Ohdo syndrome, Intellectual disability with Marfanoid habitus, FG syndrome, Opitz-Kaveggia syndrome, Lujan-Fryns syndromeXL2930
MFAP5Aortic aneurysm, familial thoracicAD23
MYH11Aortic aneurysm, familial thoracicAD/AR1648
MYLK*Aortic aneurysm, familial thoracic 7AD1628
NOTCH1Aortic valve disease, Adams-Oliver syndromeAD5696
PLOD1Ehlers-Danlos syndromeAR3041
PLOD3Bone fragility with contractures, arterial rupture, and deafnessAR33
PRKG1Aortic aneurysm, familial thoracic 8AD23
SKIShprintzen-Goldberg syndromeAD2023
SLC2A10Arterial tortuosity syndromeAR2334
SLC39A13Spondylodysplastic Ehlers-Danlos syndromeAR29
SMAD2Loeys-Dietz syndrome, Congenital heart defects, nonsyndromicAD413
SMAD3Aneurysms-osteoarthritis syndrome, Loeys-Dietz syndromeAD4882
SMAD4Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Polyposis, juvenile intestinal, Myhre dysplasia, Hereditary hemorrhagic telangiectasiaAD179143
SMAD6Craniosynostosis 7AD538
TGFB2Loeys-Dietz syndromeAD3638
TGFB3Loeys-Dietz syndrome (Reinhoff syndrome), Arrhythmogenic right ventricular dysplasiaAD1926
TGFBR1Loeys-Dietz syndromeAD4069
TGFBR2Loeys-Dietz syndromeAD58139
ZDHHC9Mental retardation, syndromic, RaymondXL914
#

The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads), and/or the gene has exons listed under Test limitations section that are not included in the panel as they are not sufficiently covered with high quality sequence reads.

*

Some, or all, of the gene is duplicated in the genome. Read more.

The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#). Due to possible limitations these genes may not be available as single gene tests.

Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), mitochondrial (mi), X-linked (XL), X-linked dominant (XLD) and X-linked recessive (XLR); ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database (ClinVar); HGMD refers to the number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD). The list of associated, gene specific phenotypes are generated from CGD or Mitomap databases.

Non-coding variants covered by Aorta Panel

To view complete table content, scroll horizontally.

GeneGenomic location HG19HGVSRefSeqRS-number
ABCC6Chr16:16244424c.4403+11C>GNM_001171.5rs72664215
ABCC6Chr16:16256835c.3506+15G>ANM_001171.5rs72664302
ABCC6Chr16:16281097c.1780-29T>ANM_001171.5rs72664206
ABCC6Chr16:16284246c.1432-22C>ANM_001171.5rs72664297
ATP7AChrX:77279056c.2916+2480T>GNM_000052.5
ATP7AChrX:77287843c.3294+763C>GNM_000052.5
CBSChr21:44496326c.-86_-85+8delAGGTAGAAGANM_001178008.1
COL1A1Chr17:48266910c.2668-11T>GNM_000088.3rs786205505
COL1A1Chr17:48267594c.2451+94G>TNM_000088.3
COL1A1Chr17:48267611c.2451+77C>TNM_000088.3rs72651665
COL1A1Chr17:48268147c.2343+31T>ANM_000088.3
COL1A1Chr17:48272201c.1354-12G>ANM_000088.3rs72648337
COL1A1Chr17:48273368c.1003-43_1003-32delTGCCATCTCTTCNM_000088.3rs72645359
COL1A1Chr17:48273574c.958-18_958-15delTTCCNM_000088.3rs72645351
COL1A1Chr17:48273742c.904-14G>ANM_000088.3
COL1A1Chr17:48273743c.904-15T>ANM_000088.3
COL1A2Chr7:94025130c.70+717A>GNM_000089.3rs72656354
COL1A2Chr7:94030856c.226-22_226-11delTTTTTTTTTTTTNM_000089.3
COL2A1Chr12:48379984c.1527+135G>ANM_001844.4
COL3A1Chr2:189872183c.3256-43T>GNM_000090.3rs587779667
COL4A5ChrX:107813924c.385-719G>ANM_033380.2rs104886396
COL4A5ChrX:107816792c.466-12G>ANM_033380.2rs104886414
COL4A5ChrX:107820077c.609+875G>TNM_033380.2
COL4A5ChrX:107821295c.646-12_646-11delTTNM_033380.2rs104886436
COL4A5ChrX:107834930c.1423+57dupCNM_033380.2rs104886328
COL4A5ChrX:107838719c.1424-20T>ANM_033380.2rs281874668
COL4A5ChrX:107842994c.1948+894C>GNM_033380.2
COL4A5ChrX:107845097c.2042-18A>GNM_033380.2rs104886341
COL4A5ChrX:107849932c.2245-40A>GNM_033380.2
COL4A5ChrX:107849958c.2245-14T>ANM_033380.2
COL4A5ChrX:107852872c.2395+2750A>GNM_033380.2
COL4A5ChrX:107908726c.3374-11C>ANM_033380.2rs104886387
COL4A5ChrX:107933678c.4529-2300T>GNM_033380.2
COL4A5ChrX:107935633c.4529-345A>GNM_033380.2
COL4A5ChrX:107938272c.4821+121T>CNM_033380.2rs104886423
COL4A5ChrX:107938337c.4822-152dupTNM_033380.2
COL4A5ChrX:107938346c.4822-151_4822-150insTNM_033380.2rs397515494
COL5A1Chr9:137645685c.1720-11T>ANM_000093.4rs863223444
COL5A1Chr9:137680989c.2647-12A>GNM_000093.4
COL5A1Chr9:137686903c.2701-25T>GNM_000093.4rs765079080
COL5A1Chr9:137726806c.5137-11T>ANM_000093.4rs183495554
COL5A2Chr2:189927655c.1924-11T>CNM_000393.3
ELNChr7:73480347c.2272+20C>GNM_001278939.1
FBN1Chr15:48707358c.8051+375G>TNM_000138.4
FBN1Chr15:48720682c.6872-14A>GNM_000138.4
FBN1Chr15:48721629c.6872-961A>GNM_000138.4
FBN1Chr15:48739106c.5672-87A>GNM_000138.4
FBN1Chr15:48739107c.5672-88A>GNM_000138.4
FBN1Chr15:48764885c.4211-32_4211-13delGAAGAGTAACGTGTGTTTCTNM_000138.4
FBN1Chr15:48786466c.2678-15C>ANM_000138.4
FBN1Chr15:48802380c.1589-14A>GNM_000138.4
FBN1Chr15:48818478c.863-26C>TNM_000138.4
FBN2Chr5:127670560c.3974-24A>CNM_001999.3
FBN2Chr5:127670562c.3974-26T>GNM_001999.3
FBN2Chr5:127671284c.3725-15A>GNM_001999.3
FLNAChrX:153581587c.6023-27_6023-16delTGACTGACAGCCNM_001110556.1
GATA5Chr20:61051165c.-201A>GNM_080473.4
GATA5Chr20:61051462NM_080473.4rs1193866928
SMAD2Chr18:45396947c.237-12A>GNM_005901.5
TGFB3Chr14:76425035c.*495C>TNM_003239.2rs387906514
TGFB3Chr14:76447266c.-30G>ANM_003239.2rs770828281
TGFBR2Chr3:30648317c.-59C>TNM_001024847.2

Test Strengths

The strengths of this test include:

  • CAP accredited laboratory
  • CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory
  • Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance
  • Careful construction of clinically effective and scientifically justified gene panels
  • Some of the panels include the whole mitochondrial genome (please see the Panel Content section)
  • Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level
  • ~2,000 non-coding disease causing variants in our clinical grade NGS assay for panels (please see ‘Non-coding disease causing variants covered by this panel’ in the Panel Content section)
  • Our rigorous variant classification scheme
  • Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data
  • Our comprehensive clinical statements

Test Limitations

The following exons are not included in the panel as they are not sufficiently covered with high quality sequence reads: *ADAMTS2* (NM_021599:11), *B3GAT3* (NM_001288722:5). Genes with suboptimal coverage in our assay are marked with number sign (#) and genes with partial, or whole gene, segmental duplications in the human genome are marked with an asterisk (*) if they overlap with the UCSC pseudogene regions. Gene is considered to have suboptimal coverage when >90% of the gene’s target nucleotides are not covered at >20x with mapping quality score (MQ>20) reads. The technology may have limited sensitivity to detect variants in genes marked with these symbols (please see the Panel content table above).

This test does not detect the following:

  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Some of the panels include the whole mitochondrial genome but not all (please see the Panel Content section)
  • Repeat expansion disorders unless specifically mentioned
  • Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above Panel Content / non-coding variants covered by the panel).

This test may not reliably detect the following:

  • Low level mosaicism in nuclear genes (variant with a minor allele fraction of 14.6% is detected with 90% probability)
  • Stretches of mononucleotide repeats
  • Low level heteroplasmy in mtDNA (>90% are detected at 5% level)
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Some disease causing variants present in mtDNA are not detectable from blood, thus post-mitotic tissue such as skeletal muscle may be required for establishing molecular diagnosis.

The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section.

The genes on the panel have been carefully selected based on scientific literature, mutation databases and our experience.

Our panels are sectioned from our high-quality, clinical grade NGS assay. Please see our sequencing and detection performance table for details regarding our ability to detect different types of alterations (Table).

Assays have been validated for various sample types including EDTA-blood, isolated DNA (excluding from formalin fixed paraffin embedded tissue), saliva and dry blood spots (filter cards). These sample types were selected in order to maximize the likelihood for high-quality DNA yield. The diagnostic yield varies depending on the assay used, referring healthcare professional, hospital and country. Plus analysis increases the likelihood of finding a genetic diagnosis for your patient, as large deletions and duplications cannot be detected using sequence analysis alone. Blueprint Genetics’ Plus Analysis is a combination of both sequencing and deletion/duplication (copy number variant (CNV)) analysis.

The performance metrics listed below are from an initial validation performed at our main laboratory in Finland. The performance metrics of our laboratory in Marlborough, MA, are equivalent.

Performance of Blueprint Genetics high-quality, clinical grade NGS sequencing assay for panels.

Sensitivity % (TP/(TP+FN)Specificity %
Single nucleotide variants99.89% (99,153/99,266)>99.9999%
Insertions, deletions and indels by sequence analysis
1-10 bps99.2% (7,745/7,806)>99.9999%
11-50 bps99.13% (2,524/2,546)>99.9999%
Copy number variants (exon level dels/dups)
1 exon level deletion (heterozygous)100% (20/20)NA
1 exon level deletion (homozygous)100% (5/5)NA
1 exon level deletion (het or homo)100% (25/25)NA
2-7 exon level deletion (het or homo)100% (44/44)NA
1-9 exon level duplication (het or homo)75% (6/8)NA
Simulated CNV detection
5 exons level deletion/duplication98.7%100.00%
Microdeletion/-duplication sdrs (large CNVs, n=37))
Size range (0.1-47 Mb)100% (25/25)
   
The performance presented above reached by Blueprint Genetics high-quality, clinical grade NGS sequencing assay with the following coverage metrics
   
Mean sequencing depth143X
Nucleotides with >20x sequencing coverage (%)99.86%

Performance of Blueprint Genetics Mitochondrial Sequencing Assay.

Sensitivity %Specificity %
ANALYTIC VALIDATION (NA samples; n=4)
Single nucleotide variants
Heteroplasmic (45-100%)100.0% (50/50)100.0%
Heteroplasmic (35-45%)100.0% (87/87)100.0%
Heteroplasmic (25-35%)100.0% (73/73)100.0%
Heteroplasmic (15-25%)100.0% (77/77)100.0%
Heteroplasmic (10-15%)100.0% (74/74)100.0%
Heteroplasmic (5-10%)100.0% (3/3)100.0%
Heteroplasmic (<5%)50.0% (2/4)100.0%
CLINICAL VALIDATION (n=76 samples)
All types
Single nucleotide variants n=2026 SNVs
Heteroplasmic (45-100%)100.0% (1940/1940)100.0%
Heteroplasmic (35-45%)100.0% (4/4)100.0%
Heteroplasmic (25-35%)100.0% (3/3)100.0%
Heteroplasmic (15-25%)100.0% (3/3)100.0%
Heteroplasmic (10-15%)100.0% (9/9)100.0%
Heteroplasmic (5-10%)92.3% (12/13)99.98%
Heteroplasmic (<5%)88.9% (48/54)99.93%
Insertions and deletions by sequence analysis n=40 indels
Heteroplasmic (45-100%) 1-10bp100.0% (32/32)100.0%
Heteroplasmic (5-45%) 1-10bp100.0% (3/3)100.0%
Heteroplasmic (<5%) 1-10bp100.0% (5/5)99,997%
SIMULATION DATA /(mitomap mutations)
Insertions, and deletions 1-24 bps by sequence analysis; n=17
Homoplasmic (100%) 1-24bp100.0% (17/17)99.98%
Heteroplasmic (50%)100.0% (17/17)99.99%
Heteroplasmic (25%)100.0% (17/17)100.0%
Heteroplasmic (20%)100.0% (17/17)100.0%
Heteroplasmic (15%)100.0% (17/17)100.0%
Heteroplasmic (10%)94.1% (16/17)100.0%
Heteroplasmic (5%)94.1% (16/17)100.0%
Copy number variants (separate artifical mutations; n=1500)
Homoplasmic (100%) 500 bp, 1kb, 5 kb100.0%100.0%
Heteroplasmic (50%) 500 bp, 1kb, 5 kb100.0%100.0%
Heteroplasmic (30%) 500 bp, 1kb, 5 kb100.0%100.0%
Heteroplasmic (20%) 500 bp, 1kb, 5 kb99.7%100.0%
Heteroplasmic (10%) 500 bp, 1kb, 5 kb99.0%100.0%
The performance presented above reached by following coverage metrics at assay level (n=66)
Mean of mediansMedian of medians
Mean sequencing depth MQ0 (clinical)18224X17366X
Nucleotides with >1000x MQ0 sequencing coverage (%) (clinical)100%
rho zero cell line (=no mtDNA), mean sequencing depth12X

The target region for each gene includes coding exons and ±20 base pairs from the exon-intron boundary. In addition, the panel includes non-coding and regulatory variants if listed above (Non-coding variants covered by the panel). Some regions of the gene(s) may be removed from the panel if specifically mentioned in the ‘Test limitations” section above. If the test includes the mitochondrial genome the target region gene list contains the mitochondrial genes. The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. Our pipeline is streamlined to maximize sensitivity without sacrificing specificity. We have incorporated a number of reference population databases and mutation databases including, but not limited, to 1000 Genomes Project, gnomAD, ClinVar and HGMD into our clinical interpretation software to make the process effective and efficient. For missense variants, in silico variant prediction tools such as  SIFT, PolyPhen,MutationTaster are used to assist with variant classification. Through our online ordering and statement reporting system, Nucleus, ordering providers have access to the details of the analysis, including patient specific sequencing metrics, a gene level coverage plot and a list of regions with suboptimal coverage (<20X for nuclear genes and <1000X for mtDNA) if applicable. This reflects our mission to build fully transparent diagnostics where ordering providers can easily visualize the crucial details of the analysis process.

We provide customers with comprehensive clinical report available on the market. Clinical interpretation requires a fundamental understanding of clinical genetics and genetic principles. At Blueprint Genetics, our Ph.D. molecular geneticists, medical professionals, and other highly experienced experts prepare clinical reports by evaluating the identified variants in the context of the phenotypic information provided in the requisition form.

Our goal is to provide clinically meaningful reports that are understandable for all medical professionals regardless of whether they have formal training in genetics. Variant classification is the cornerstone of clinical interpretation and resulting patient management decisions. Our classifications follow the ACMG guideline 2015. Sequence and copy number variants classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS) are confirmed using bidirectional Sanger sequencing or by orthogonal methods such as qPCR/ddPCR when they do not meet our stringent NGS quality metrics for a true positive call.

Our clinical report includes tables for sequence and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, phenotypes, and classification of the variant). In addition, the statement includes detailed descriptions of the variant, gene, and phenotype(s), including the role of the specific gene in human disease, the mutation profile, information about the gene’s variation in population cohorts, and detailed information about related phenotypes. We also provide links to the references, abstracts, and variant databases used to help ordering providers further evaluate the reported findings if desired.

The panel report is divided into primary findings and additional findings sections. Variants reported as primary findings are known disease-causing variants or rare variants that could potentially explain the patient’s phenotype as described to the laboratory at the time of interpretation. The conclusion summarizes all the existing information and provides our rationale for the classification of the variant.

Variants reported as additional findings are variants that are not likely or sufficient to cause the tested patient’s phenotype, based on the current knowledge. Additional findings in panel reports include variants that are, for example, carrierships of single heterozygous variants in genes associated with autosomal recessive disorders, variants of uncertain significance in genes associated with autosomal dominant disorders (if pathogenic or likely pathogenic variants considered sufficient to explain the patient’s phenotype are reported as primary findings), or risk alleles identified in genes included in the panel.

Identification of pathogenic or likely pathogenic variants in dominant disorders or their combinations in different alleles in recessive disorders are considered molecular confirmation of the clinical diagnosis. In these cases, family member testing can be used for risk stratification. We do not recommend using variants of uncertain significance (VUS) for family member risk stratification or patient management. Genetic counseling is recommended.

Our interpretation team analyzes millions of variants from thousands of individuals with rare diseases. Our internal database and our understanding of variants and related phenotypes increases with every case analyzed. Our laboratory is therefore well positioned to reclassify previously reported variants as new information becomes available. If a variant previously reported as a primary or secondary finding by Blueprint Genetics is reclassified so that it becomes diagnostic (VUS to P/LP) or earlier molecular diagnosis is removed (P/LP to VUS, LB, B), our laboratory will issue a follow-up statement to the original ordering healthcare provider at no additional cost.