- Is a 125 gene panel that includes assessment of non-coding variants.
Is ideal for patients with congenital heart disease, particularly those with features of hereditary disorders.
Is not ideal for patients suspected to have a ciliopathy or a rasopathy. For those patients, please consider our Primary Ciliary Dyskinesia Panel and our Noonan Syndrome Panel, respectively.
The Blueprint Genetics Congenital Structural Heart Disease Panel (test code CA1501):
Read about our accreditations, certifications and CE-marked IVD medical devices here.
Refer to the most current version of ICD-10-CM manual for a complete list of ICD-10 codes.
- 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.
There are many types of congenital heart disease (CHD) ranging from simple asymptomatic defects to complex defects with severe, life-threatening symptoms. CHDs are the most common type of birth defect and affect at least 8 out of every 1,000 newborns. Annually, more than 35,000 babies in the United States are born with CHDs. Many of these CHDs are simple conditions and need no treatment or are easily repaired. Some babies are born with complex CHD requiring special medical care. The diagnosis and treatment of complex CHDs has greatly improved over the past few decades. As a result, almost all children who have complex heart defects survive to adulthood and can live active, productive lives. However, many patients who have complex CHDs continue to need special heart care throughout their lives. In the United States, more than 1 million adults are living with congenital heart disease.
Genes in the Congenital Structural Heart Disease Panel and their clinical significance
|ABL1||Congenital heart defects and skeletal malformations syndrome (CHDSKM)||AD||30||5|
|ACTA2||Aortic aneurysm, familial thoracic, Moyamoya disease, Multisystemic smooth muscle dysfunction syndrome||AD||20||76|
|ACTC1||Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Atrial septal defect, Dilated cardiomyopathy (DCM)||AD||23||63|
|ACTG1*||Deafness, Baraitser-Winter syndrome||AD||27||47|
|ACVR1||Fibrodysplasia ossificans progressiva||AD||14||19|
|ACVR2B||Heterotaxy, visceral, 4, autosomal||AD||1||2|
|AFF4||Cognitive impairment, coarse facies, Heart defects, Obesity, Pulmonary involvement, Short stature, and skeletal dysplasia (CHOPS syndrome)||AD||3||3|
|AMMECR1||Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis||XL||4||5|
|ARID1A||Coffin-Siris syndrome, Mental retardation||AD||27||35|
|ARID1B||Coffin-Siris syndrome, Mental retardation||AD||153||185|
|B3GAT3#*||Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects||AR||6||13|
|BCOR||Microphthalmia, syndromic, Oculofaciocardiodental syndrome||XL||40||53|
|BMPR2||Pulmonary hypertension, primary, Pulmonary venoocclusive disease||AD||391||572|
|BRAF*||LEOPARD syndrome, Noonan syndrome, Cardiofaciocutaneous syndrome||AD||134||65|
|C12ORF57||Corpus callosum hypoplasia, recessive, Temtamy syndrome||AR||7||6|
|C2CD3||Orofaciodigital syndrome XIV||AR||9||10|
|CASZ1||Dilated cardiomyopathy (DCM), Ventricular septal defect||AD||3||2|
|CBL||Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia||AD||24||43|
|CDK13||Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder||AD||13||20|
|CDKN1C||Beckwith-Wiedemann syndrome, IMAGE syndrome||AD||35||81|
|CFAP53||Heterotaxy, visceral, 6, autosomal recessive||AR||4||4|
|CHD7||Isolated gonadotropin-releasing hormone deficiency, CHARGE syndrome||AD||276||860|
|CHRM2||Dilated cardiomyopathy (DCM)||AD/AR||1|
|CRELD1||Atrioventricular septal defect, partial, with or without heterotaxy||AD||2||16|
|CTC1||Cerebroretinal microangiopathy with calcifications and cysts||AR||21||33|
|EFTUD2||Mandibulofacial dysostosis with microcephaly, Esophageal atresia, syndromic||AD||45||99|
|EIF2AK4||Pulmonary venoocclusive disease||AR||27||84|
|ELN||Cutis laxa, Supravalvular aortic stenosis||AD||78||113|
|ENG||Juvenile polyposis syndrome, Hereditary hemorrhagic telangiectasia||AD||158||491|
|EVC||Weyers acrofacial dysostosis, Ellis-van Creveld syndrome||AD/AR||58||83|
|EVC2||Ellis-van Creveld syndrome, Weyers acrodental dysostosis||AD/AR||78||75|
|FKTN||Muscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle)||AD/AR||45||58|
|FLNA||Frontometaphyseal 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-linked||XL||133||257|
|FLT4||Lymphedema, hereditary I (Milory disease)||AD/AR||11||85|
|FOXC1||Axenfeld-Rieger syndrome, Iridogoniodysgenesis, Peters anomaly||AD||46||135|
|FOXF1||Alveolar capillary dysplasia with misalignment of pulmonary veins||AD||10||102|
|FOXH1||Congenital heart malformations, Holoprosencephaly||AD||33|
|FOXP1||Mental retardation with language impairment and autistic features, Congenital heart malformations||AD||48||76|
|GATA4*||Tetralogy of Fallot, Atrioventricular septal defect, Testicular anomalies with or without congenital heart disease, Ventricular septal defect, Atrial septal defect||AD||37||140|
|GATA5||Familial atrial fibrillation, Tetralogy of Fallot, Single ventricular septal defect||AD||5||32|
|GATA6||Heart defects, congenital, and other congenital anomalies, Atrial septal defect 9, atrioventricular septal defect 5, Persistent truncus arteriosus, Tetralogy of Fallot||AD||16||82|
|GDF1||Transposition of the great arteries, dextro-looped 3, Double-outlet right ventricle||AR||11||15|
|GJA1*||Oculodentodigital dysplasia mild type, Oculodentodigital dysplasia severe type, Syndactyly type 3||AD/AR||31||107|
|GJA5||Progressive familial heart block, Atrial standstill, digenic, Atrial fibrillation||AD/Digenic||8||34|
|HAND1||Congenital heart defects, Dilated cardiomyopathy||AD||9|
|HAND2||Dilated cardiomyopathy (DCM), Congenital heart malformations||AD||2||5|
|HDAC8||Cornelia de Lange syndrome||XL||41||50|
|HOXA1||Athabaskan brainstem dysgenesis syndrome, Bosley-Salih-Alorainy syndrome||AR||4||7|
|HRAS||Costello syndrome, Congenital myopathy with excess of muscle spindles||AD||43||31|
|KRAS*||Noonan syndrome, Cardiofaciocutaneous syndrome||AD||63||35|
|KYNU||Hydroxykynureninuria, Vertebral, cardiac, renal, and limb defects syndrome 2||AR||4||7|
|LEFTY2*||Left-right axis malformations||AD||1||3|
|LZTR1||Schwannomatosis, Noonan syndrome||AD/AR||34||71|
|MED12||Ohdo syndrome, Mental retardation, with Marfanoid habitus, FG syndrome, Opitz-Kaveggia syndrome, Lujan-Fryns syndrome||XL||29||30|
|MED13L||Transposition of the great arteries, dextro-looped 1, Mental retardation and distinctive facial features with or without cardiac defects, Congenital heart defects and intellectual disability, Intellectual disability, autosomal recessive||AD/AR||92||78|
|MEGF8||Carpenter syndrome 2||AR||6||14|
|MEIS2||Cleft palate, cardiac defects, and mental retardation (CPCMR)||AD||10||18|
|MMP21||Heterotaxy, visceral, 7||AR||4||18|
|MYO18B||Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism||AR||2||4|
|MYRF||Congenital heart malformations, Congenital abnormalities of the kidney and urinary tract||AD||1||1|
|NAA15||Congenital heart malformations||AD||10||32|
|NEXN||Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM)||AD||6||43|
|NF1*||Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndrome||AD||1157||2901|
|NIPBL||Cornelia de Lange syndrome||AD||311||425|
|NKX2-5||Conotruncal heart malformations, Hypothyroidism, congenital nongoitrous,, Atrial septal defect, Ventricular septal defect 3, Conotruncal heart malformations, variable, Tetralogy of Fallot||AD||45||108|
|NKX2-6||Persistent truncus arteriosus, Conotruncal heart malformations||AD/AR||2||9|
|NONO||Mental retardation, X-linked, syndrome 34, Left ventricular non-compaction cardiomyopathy (LVNC)||XL||10||4|
|NOTCH1||Aortic valve disease, Adams-Oliver syndrome||AD||56||96|
|NOTCH2*||Alagille syndrome, Hajdu-Cheney syndrome||AD||37||70|
|NR2F2||Congenital heart defects, multiple types, 4||AD||12||16|
|NSD1||Sotos syndrome, Weaver syndrome, Beckwith-Wiedemann syndrome||AD||329||517|
|PITX2||Axenfeld-Rieger syndrome, Ring dermoid of cornea, Iridogoniodysgenesis, Peters anomaly||AD||23||101|
|PKD1L1||Heterotaxy, visceral, 8, autosomal||AR||2||6|
|PLD1||Cardiac valvular defect, developmental||4||4|
|PPP1CB||Noonan syndrome-like disorder with loose anagen hair 2||AD||8||11|
|PRDM6||Patent ductus arteriosus 3, Congenital heart malformations||AD||4||3|
|PRKD1||Congenital heart defects and ectodermal dysplasia||AD||2||7|
|PTPN11||Noonan syndrome, Metachondromatosis||AD||135||140|
|PUF60||Short stature, Microcephaly||AD||24||30|
|RAB23||Carpenter syndrome 1||AR||5||15|
|RAF1||LEOPARD syndrome, Noonan syndrome, Dilated cardiomyopathy (DCM)||AD||45||53|
|RECQL4||Baller-Gerold syndrome, RAPADILINO syndrome, Rothmund-Thomson syndrome||AR||82||114|
|RERE*||Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH)||AD||24||24|
|SALL4||Acro-renal-ocular syndrome, Duane-radial ray/Okihiro syndrome||AD||21||56|
|SMARCB1||Schwannomatosis, Rhabdoid tumor predisposition syndrome, Coffin-Siris syndrome 3||AD||36||118|
|SMC1A||Cornelia de Lange syndrome||XL||73||87|
|SMC3||Cornelia de Lange syndrome||AD||25||21|
|SOS2||Noonan syndrome 9||AD||4||6|
|STAG2||Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder||XL||6||14|
|STRA6||Microphthalmia, syndromic, Microphthalmia, isolated, with coloboma||AR||22||33|
|TAB2||Congenital heart defects, multiple types, 2||AD||13||31|
|TBX1||Conotruncal anomaly face syndrome||AD||17||72|
|TBX20*||Atrial septal defect 4||AD||4||28|
|TFAP2B||Patent ductus arteriosus, nonsyndromic, Char syndrome||AD||10||12|
|TLL1||Atrial septal defect||AD||3||7|
|TMEM94||Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH)||AR||3|
|TWIST1||Saethre-Chotzen syndrome, Robinow-Sorauf syndrome, Craniosynostosis||AD||28||205|
|ZFPM2||46,XY sex reversal, Diaphragmatic hernia 3, Tetralogy of Fallot||AD/AR||9||50|
|ZIC3||Heterotaxy, visceral, VACTERL association, Congenital heart defects, nonsyndromic||XL||15||41|
* Some, or all, of the gene is duplicated in the genome. Read more.
# 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.
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 Congenital Structural Heart Disease Panel
|Gene||Genomic location HG19||HGVS||RefSeq||RS-number|
Added and removed genes from the panel
|Genes added||Genes removed|
|C2CD3 CASZ1 CDKN1C FKTN FLT4 LZTR1 MEGF8 NEXN PLD1 RECQL4 TWIST1|
- 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
- Our publicly available analytic validation demonstrating complete details of test performance
- ~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
The following exons are not included in the panel as they are not sufficiently covered with high quality sequence reads: 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).
- 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).
- 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 and see our Analytic Validation.
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 Seattle, WA, are equivalent.
Performance of Blueprint Genetics high-quality, clinical grade NGS sequencing assay for panels.
|Sensitivity % (TP/(TP+FN)||Specificity %|
|Single nucleotide variants||99.89% (99,153/99,266)||>99.9999%|
|Insertions, deletions and indels by sequence analysis|
|1-10 bps||99.2% (7,745/7,806)||>99.9999%|
|11-50 bps||99.13% (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/duplication||98.7%||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 depth||143X|
|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)|
|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%) 1-10bp||100.0% (32/32)||100.0%|
|Heteroplasmic (5-45%) 1-10bp||100.0% (3/3)||100.0%|
|Heteroplasmic (<5%) 1-10bp||100.0% (5/5)||99,997%|
|SIMULATION DATA /(mitomap mutations)|
|Insertions, and deletions 1-24 bps by sequence analysis; n=17|
|Homoplasmic (100%) 1-24bp||100.0% (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 kb||100.0%||100.0%|
|Heteroplasmic (50%) 500 bp, 1kb, 5 kb||100.0%||100.0%|
|Heteroplasmic (30%) 500 bp, 1kb, 5 kb||100.0%||100.0%|
|Heteroplasmic (20%) 500 bp, 1kb, 5 kb||99.7%||100.0%|
|Heteroplasmic (10%) 500 bp, 1kb, 5 kb||99.0%||100.0%|
|The performance presented above reached by following coverage metrics at assay level (n=66)|
|Mean of medians||Median of medians|
|Mean sequencing depth MQ0 (clinical)||18224X||17366X|
|Nucleotides with >1000x MQ0 sequencing coverage (%) (clinical)||100%|
|rho zero cell line (=no mtDNA), mean sequencing depth||12X|
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 the most comprehensive clinical report available on the market. Clinical interpretation requires a fundamental understanding of clinical genetics and genetic principles. At Blueprint Genetics, our PhD molecular geneticists, medical geneticists and clinical consultants prepare the clinical statement together by evaluating the identified variants in the context of the phenotypic information provided in the requisition form. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals regardless of whether they have formal training in genetics.
Variant classification is the corner stone of clinical interpretation and resulting patient management decisions. Our classifications follow the ACMG guideline 2015.
The final step in the analysis is orthogonal confirmation. Sequence and copy number variants classified as pathogenic, likely pathogenic and variants of uncertain significance (VUS) are confirmed using bi-directional 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 statement includes tables for sequencing and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, OMIM 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 conclusion summarizes all of the existing information and provides our rationale for the classification of the variant.
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 re-classify previously reported variants as new information becomes available. If a variant previously reported by Blueprint Genetics is re-classified, our laboratory will issue a follow-up statement to the original ordering health care provider at no additional cost.