Familial Variant Testing

Summary
  • Diagnostic testing in affected family members
  • Predictive testing in unaffected family members
  • Carrier testing in the case of autosomal recessive and X-linked disorders
  • Segregation of variants

With Familial Variant Testing, you can order for up to 10 variants per order for a fixed price.

Blueprint Genetics will only report the variant(s) of interest. If the individual being tested is suspected of being affected with an inherited disorder, then another more comprehensive test (single gene, panel, WES) may be appropriate.

All variants, both nuclear and mitochondrial, that were previously identified at Blueprint Genetics are eligible for this service. Most variants detected by other laboratories are also eligible unless being repeat expansions, mitochondrial or small CNVs.

Please contact your local Genetic Services Consultant or our Customer Support team to assist with ordering. We are here to help you!

Availability

4 weeks

CPT code *
See below **
Test code

FVT001

* 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.
** CPT coding is dependent on gene requested and analyzed.

Summary

The Blueprint Genetics Familial Variant Testing (test code FVT001):

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.

  • Diagnostic testing in affected family members
  • Predictive testing in unaffected family members
  • Carrier testing in the case of autosomal recessive and X-linked disorders
  • Segregation of variants

With Familial Variant Testing, you can order for up to 10 variants per order for a fixed price.

Blueprint Genetics will only report the variant(s) of interest. If the individual being tested is suspected of being affected with an inherited disorder, then another more comprehensive test (single gene, panel, WES) may be appropriate.

All variants, both nuclear and mitochondrial, that were previously identified at Blueprint Genetics are eligible for this service. Most variants detected by other laboratories are also eligible unless being repeat expansions, mitochondrial or small CNVs.

Please contact your local Genetic Services Consultant or our Customer Support team to assist with ordering. We are here to help you!

Test strengths

  • 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
  • Comprehensive clinical statement

Test limitations

  • Familial Variant Testing for mitochondrial variants, CNVs and testing of prenatal samples are only available for cases where the index patient was tested at Blueprint Genetics.
  • Familial Variant Testing for mitochondrial variants is not available for prenatal samples.

For further information on limitations, please contact our Support team.

Familial Variant Testing may not reliably detect the following:

  • Low level mosaicism

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.

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)
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%) 1-10bp 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
  • Log in to our online portal Nucleus at nucleus.blueprintgenetics.com for the easiest way to order and access results.
  • Fill out both the consent and requisition forms.
  • Send the sample to Blueprint Genetics.
    • Sample Requirements:
      • Blood (min. 1ml) in an EDTA tube
      • Extracted DNA, min. 2 μg in TE buffer or equivalent
      • Saliva (Please see the accepted saliva kits on our Sample Requirements page)
    • Sending a positive control sample from the index patient is not required.

Familial Variant Testing is done with Next Generation Sequencing (NGS) technology and/or Sanger sequencing and dPCR.

To provide more flexibility, we have extended the time for receiving samples for our 5 Free FVT service during the COVID-19 period. As previously, the orders need to be placed within 90 days from report, but if you have challenges receiving all samples by that time, you can still send your samples after the 100 days by using the promotion code “BPG150FVT”. Samples can be sent within 150 days. The extension is available until December 31, 2020. All other eligibility criteria will remain the same.

Five family members are eligible for free testing for up to 10 variants. Eligibility criteria are as follows:

    • The proband had a panel test performed at Blueprint Genetics.
    • The variant(s) being tested must be classified as either pathogenic, likely pathogenic, or as a variant of uncertain significance and be reported in the primary variant table in the clinical statement. Variants reported in the additional findings table are not eligible for free family variant testing but can be tested as part of our variant specific testing service.
    • The individuals are blood relatives of the proband.
    • The FVT orders are placed within 90 days and samples are received within 100 days of the proband’s result (Use the promotion code “BPG150FVT” to extend from 100 days to 150 days).
    • The order is inputted via the normal FVT ordering page or paper requisition and the eligibility is checked automatically.

Subscribe to our newsletter

Subscribe