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At the 2025 American College of Medical Genetics and Genomics (ACMG) annual meeting in Los Angeles, we hosted a focused session on the role of exome and whole genome sequencing (WGS) in clinical and research settings. The goal was to spark conversation about available technologies, implementation challenges, and future strategies. Four expert speakers shared insights on clinical utility, followed by a lively audience Q&A.
This blog captures key takeaways from the event, including when and why broader testing is preferred over targeted panels, how to optimize virtual panels, and reimbursement realities. Whether you’re a lab director, clinician, or genetic counselor, these insights offer timely guidance.
Historically, targeted panels have been the cornerstone of many diagnostic workflows. However, as our understanding of gene-disease associations evolves, so too must our approach to testing.
Exome sequencing can adapt to the dynamic nature of clinical genetics. Take carrier screening, for example. As Mahmoud Aarabi, Medical Director of UPMC Cytogenetics Laboratories, explained, the list of genes recommended for autosomal recessive and X-linked carrier screening by ACMG1 is continuously updated based on new phenotypic and population data. Rather than continually revising panel content, exome sequencing provides a flexible, future-ready alternative. Phenotyping also plays a critical role. In prenatal testing, complete phenotyping can boost exome diagnostic yield by 7–10%.2
Jeanette McCarthy, Principal Consultant at Zifo, emphasized how labs can maximize efficiency using virtual panels (slice panels) to analyze exome data. With this approach, labs validate the wet lab component once and can then revise gene content as needed without extensive revalidation.
But designing virtual panels well requires careful forethought. She recommended selecting only genes with robust disease-gene validity, accounting for technically challenging targets (e.g., SMN1, PMS2), and avoiding copy number variation (CNV) analysis for genes that lack sufficient evidence of a loss-of-function mechanism. Additionally, genes should be excluded when the only relevant variant types cannot be reliably detected by exome sequencing - for example, including ATXN7 is unhelpful due to exomes’ inability to detect repeat expansions.
Exome sequencing consistently delivers higher diagnostic yield and cost savings compared to traditional approaches
Joe Jacher, Genomenon and trained genetic counselor, highlighted the clinical and economic case. “You can save $20,000 by skipping from microarray straight to exome,” he noted, citing peer-reviewed research.3 Indeed, the literature supports exomes/genomes as first- or second-tier tests for congenital anomalies or intellectual disability.4 For neurodevelopmental disorders (NDDs), exome sequencing outperforms chromosomal microarray analysis in both diagnostic yield and cost-effectiveness when used early.4,5
One of the largest challenges to broader adoption of exome and genome sequencing in clinical settings is insurance coverage. Despite proven utility, reimbursement remains inconsistent and often favors exome over genome sequencing, which is often restricted to research use.
In pediatric oncology, for example, current guidelines may still prioritize legacy tests like karyotyping and FISH over broader sequencing approaches, even when those legacy tests fall short of delivering a diagnosis.
To navigate this, some labs are adopting hybrid models. At Stanford Medicine, clinical panels are run on a genome backbone, enabling targeted reporting first, with the option for expanded analysis later if required. It also positions the lab for a future where broader genome analysis becomes more widely accepted and reimbursed.
If insurers continue to favor exomes, exome-on-genome workflows may be a practical interim solution to futureproof workflows and streamline reanalysis as new insights emerge.
WGS offers some clear technical advantages. It covers both coding and non-coding regions, provides more uniform coverage than exomes, and captures structural variants and repeat expansions with greater accuracy.
Jennefer Carter, Senior Genetic Counselor and part of the Stanford Undiagnosed Diseases Network (UDN), described how WGS delivered diagnoses in cases where exome sequencing would have failed. Among 283 Stanford UDN patients, WGS revealed diagnoses in cases involving CNVs/structural variants, repeat expansions, and non-coding variants – challenging variant types often missed by exomes.
Genome sequencing is where we’re headed - but exomes are the most practical, reimbursable, and clinically validated tool we have right now
Audience members agreed. One noted that "genome + RNASeq is the way forward," pointing to savings from eliminating multiple legacy tests. But RNASeq has its own limitations, such as with conditions affecting tissues where genes are not expressed in the blood.
Moreover, there were warnings of variability in commercial genome testing. Some labs restrict genome interpretation to just 10 bp into introns unless another variant prompts deeper review. Transparency and education are essential to ensure providers understand what their patients are receiving.
Despite historical limitations, some institutions are already shifting toward genome-first approaches. A genetic counselor from Children's Hospital Los Angeles noted that their team now defaults to WGS for most send-outs. Encouragingly, insurer coverage is improving, and third-party labs have been able to cover costs to build evidence for future reimbursement.
So, what can clinical labs and providers do today to prepare for an exome- and genome-enabled future?
While WGS promises broader insights, exome sequencing remains the most practical and reimbursable tool today. It balances diagnostic yield, cost, and flexibility, making it a strategic choice for many clinical settings.
As infrastructure, interpretation tools, and reimbursement models continue to evolve, WGS will play a growing role in routine care. But for now, optimizing the use of exomes while laying the groundwork for a genome-based future, offers the best of both worlds.
The discussion at ACMG 2025 made clear: the path to better patient outcomes lies in making high-quality genomic testing more accessible, informed, and actionable.
Visit our Rare Disorders page to learn more about SOPHiA DDM™ exome and genome solutions.
References
Please can you introduce yourself and share a bit about your role, institution, and the genetic services you provide?
I am a laboratory scientist working in the Molecular Diagnostics Laboratory at the National Children’s Hospital “Carlos Saenz-Herrera” in Costa Rica. Our laboratory serves as the national reference center for diagnosing genetic diseases in both children and adults. Additionally, we are part of the National Oncological Counseling Project, which has been operational since 2018. Within this project, we perform genetic analyses for adult participants across the country. I am part of the team responsible for conducting genetic tests, including whole exome sequencing and Sanger sequencing, as well as analyzing, interpreting, and reporting variants. Our laboratory collaborates closely with clinicians from various hospital specialties, holding monthly clinical meetings to discuss complex and challenging cases. This multidisciplinary approach helps improve diagnosis and patient management.
Which SOPHiA GENETICS applications do you currently use in your work?
Currently, we use the SOPHiA DDM™ Hereditary Cancer Solution v2.0, which includes 83 genes associated with hereditary cancer, and the SOPHiA DDM™ Whole Exome Solution. We rely on the SOPHiA DDM™ Platform for variant analysis.
What are the key benefits of using the SOPHiA DDM™ Platform in your lab?
Using the SOPHiA DDM™ Platform has significantly streamlined our workflow by reducing analysis time and optimizing variant interpretation. The platform provides easy access to multiple databases directly within its interface, which simplifies data contextualization.
One of the most valued features is the ability to build our own custom database. This functionality allows us to perform intra-sample comparisons (within the same run), inter-sample comparisons (across all runs over time), and inter-laboratory comparisons using SOPHiA DDM™'s tools. This is essential for validating findings and ensuring consistency in our analyses.
Having a custom database is particularly beneficial because public databases often lack adequate information about Latin American populations, especially Costa Rican populations. By maintaining our own database, we can track allele frequencies specific to our population and analyze potential founder effects or population-specific genetic behaviors. This capability not only facilitates trend analysis over time but also enhances our ability to identify patterns and anomalies in genetic data. Such insights are invaluable for developing more precise and personalized clinical strategies tailored to our population.
Your recent research using the SOPHiA DDM™ Hereditary Cancer Solution v2.0 in Costa Rica identified a prominent founder variant in the BRCA2 gene. Can you share more about this discovery and its significance?As part of our involvement in the National Oncological Counseling Project, we have analyzed approximately 1500 probands and 2300 relatives since 2018. Among these families, around 800 have hereditary breast/ovarian cancer syndrome. Notably, we observed that 43% of families diagnosed with breast/ovarian cancer have a pathogenic variant in BRCA2. Of these families with BRCA2 variants, 61% carry the c.9235delG variant.
This variant does not fall within regions typically associated with breast or ovarian cancer risk. Interestingly, it has also been identified in other types of cancer within Costa Rica, such as pancreatic and prostate cancer. These findings suggest a unique genetic architecture for breast and ovarian cancer in the Costa Rican population.
The discovery of this founder variant highlights the importance of understanding population-specific genetic markers to improve diagnostics.
How has your experience been working with the SOPHiA GENETICS team?
Our collaboration with SOPHiA GENETICS has been highly positive. The team is responsive and supportive, providing valuable guidance on how to maximize the platform’s functionalities for our specific needs.
Looking ahead, what excites you most about the future of genetic testing at National Children’s Hospital “Carlos Saenz-Herrera”?
Looking ahead, we are excited about the possibilities of integrating cutting-edge technologies into our laboratory workflows.
For instance:
- Optical Genome Mapping: This technology has enormous potential to revolutionize structural variant detection by providing high-resolution insights into chromosomal abnormalities.
- Somatic Sequencing: Expanding into somatic sequencing will enable us to analyze tumor-specific mutations more comprehensively.
These advancements will further enhance our ability to provide robust diagnostic solutions and personalized treatment strategies for patients across Costa Rica.
Elexandra Barboza-Arguedas and her team are a great example of how dedicated experts can combine technology and local knowledge to make a real difference. We’re proud to support their work as they continue to expand genetic testing in Costa Rica, uncovering insights that not only advance clinical insights today but help shape a more personalized, inclusive future for healthcare.
Click through to learn more about SOPHiA DDM™ exome and hereditary cancer solutions.
We are glad to host Dr. Davide Martorana, Senior Molecular Geneticist at the Medical Genetic Lab of the University-Hospital of Parma in Italy, who shared with us his institute’s experience with the adoption of the New Generation SOPHiA DDMTM Platform.
-Hello, Davide, thank you for joining us today for this spotlight! Could you please briefly introduce yourself and describe your role, institution, and the type of services you offer?
-Sure. My name is Davide Martorana, and I am a Senior Molecular Geneticist at the Medical Genetic Lab – a lab at the University Hospital of Parma in Italy.
As a Biologist, I am part of the clinical interpretation team for focused panels and clinical whole exome sequencing for subjects with a suggestive phenotype; after the genetic test, we provide reports with results interpretation.
-Could you please share with us which of the SOPHiA GENETICS applications and services are you currently using?
-We use two different SOPHiA GENETICS solutions, the Nephropathy Solutions (NES) and Hereditary Cancer Solutions (HCS), analysed with SOPHiA DDMTM
-What are the biggest benefits you see in the New Generation SOPHiA DDMTM Platform in terms of new features/ capabilities and user experience?
-First of all, I want to state that we are very happy and satisfied with this evolution of the SOPHiA DDMTM Platform. The feature I prefer is the personalization of the information flow about genetic variants; in fact, I am sure every analyst has a preferred workflow when evaluating a single variant; for example, I like to see immediately the population frequency, both in our single center and for all SOPHiA GENETICS customers; then, the ACMG-AMP classification with specified criteria.
In my opinion, this fact is very important, because when you must manage a lot of variants, it is important to focus fast on a few but essential info, then if you want there is the possibility to access several other additional info; in particular, I appreciate the extensive link-outs to other databases, which are very accurate and useful.
-Thank you for your kind words. Could you please share an example where the SOPHiA DDMTM Platform streamlined your laboratory workflows and supported your clinical research efforts?
-In a specific family, after genetic counseling of a twenty-week-old pregnant woman with a clinical diagnosis of Polycystic Kidney disease 1 - never investigated at a genetic level - we were asked to analyze the woman and the fetus with the Nephropathy solution kit.
After the analysis on the SOPHiA DDMTM Platform, we were able to detect the causative mutation in PKD1 gene in the mother but not in the fetus. The analyses were performed in just three days after receiving the biological samples, which was a very fast turnaround.
After that analysis, we realized the true potential of having an NGS kit coupled with software with fast, reliable, and accurate results, and this is just one simple example.
-It is great to see how our solutions are impacting your real-life clinical research and streamlining your decision-making when it matters the most. On the implementation side, how was your experience with the Setup program for SOPHiA DDMTM in terms of easiness, time spent on validation, and time to routine?
-In our experience, the Setup program for SOPHiA DDMTM was very fast and easy. In fact, after the training with SOPHiA customer support, we spent just a working for validating the entire process and personalizing the information flow before introducing it in the routine analysis. This is very important and efficient for the users.
-And how does your experience with the SOPHiA GENETICS customer support look like?
-I am extremely satisfied with SOPHiA GENETICS customer support because they are efficient and proactive, answering all our queries and addressing our issues in a very short time and with great competence and kindness. I would like to thank you on behalf of the entire team for that.
We would like to warmly thank Dr. Davide Martorana for joining us in this customer spotlight.
Are you interested in exploring how the New Generation SOPHiA DDM Platform can revolutionize your workflows? Check out our recent blog post here!
The term « SOPHIA » used by the speaker refers to SOPHiA GENETICS and its products. The opinions expressed during this presentation are these of the speaker and may not represent the opinions of SOPHiA GENETICS. SOPHiA GENETICS does not provide support in the validation of custom products for clinical use. SOPHiA DDM™ Dx Homologous Recombination Deficiency Solution is available as a CE-IVD product for In Vitro Diagnostic Use in the European Economic Area (EEA), the United Kingdom and Switzerland. SOPHiA GENETICS products are for Research Use Only and not for use in diagnostic procedures unless specified otherwise.
Discover how Henry Ford Health streamlined their genetic testing by moving from three separate assays to a single, powerful exome-based solution. Learn how the SOPHiA DDM™ Exome Solution v3 consolidated their workflows for hereditary cancer, cystic fibrosis, and pharmacogenetics, offering broad gene coverage with a compact assay footprint. Dive into the full story to see how this innovative approach enabled detection of SNVs, Indels, and CNVs in one comprehensive assay, simplifying their germline testing processes.
Explore this infographic summary to discover the key findings from Janin et al.’s publication on next-generation sequencing (NGS) for the diagnosis of inherited cardiac diseases.
Click here to read the full publication.
Janin A, Januel L, Cazeneuve C, Delinière A, Chevalier P, Millat G. Molecular Diagnosis of Inherited Cardiac Diseases in the Era of Next-Generation Sequencing: A Single Center's Experience Over 5 Years. Mol Diagn Ther. 2021 May;25(3):373-385.
SOPHiA GENETICS products are for research use only – not for use in diagnostic procedures.
The HGVS nomenclature guidelines are used worldwide for genetic variant interpretation but can seem complicated and difficult to understand and apply. That is why we have created this beginner’s guide to mutation nomenclature using the HGVS recommendations, with clear visual examples that break down the process into bitesize pieces.
1. What is HGVS nomenclature?
2. How to read mutation nomenclature: Breaking down the variant description
2.1 Reference sequence e.g., NM
2.2 Description of variant e.g., c.4375C>T
2.3 Predicted consequence e.g., p.(Arg1459*)
3. The 3 prime rule for mutation
4. Final thoughts and helpful tool
The Human Genome Variation Society (HGVS) nomenclature standard was developed to prevent the misinterpretation of variants in DNA, RNA, and protein sequences. The HGVS nomenclature standard is used worldwide, especially in clinical diagnostics, and is authorized by the Human Genome Organisation (HUGO).1,2
HGVS General Terminology Recommendations1
| X Do not use | ✔️ Recommended terminology |
| Mutation or polymorphism | Variant, change, allelic variant Can be used for cancer tissue: Mutation load and tumor mutation burden |
| Pathogenic | Affects function, disease-associated, phenotype-associated |
HGVS follow recognized standards for the nomenclature of DNA and RNA nucleotides, the genetic code, amino acid descriptions, and cytogenetic band position in chromosomes.3
The HGVS recommendations for mutation nomenclature state that the format of a complete variant description should first include the reference sequence, followed by the variant description, and then the predicted consequence in parentheses. For example, NM-004006.2:c.4375C>T p.(Arg1459*) (Figure 1).
The HGVS nomenclature recommendations for sequence variants state that a complete variant description should begin with the reference sequence.1 The reference sequence accession number begins with a two-letter abbreviation (explained in Table 1), followed by a multi-digit number, and finally a version number.
Table 1. Meaning of the two-letter abbreviation at the beginning of a reference sequence accession number.
| Abbreviation | Reference sequence based on a: |
| NC | Chromosome |
| NG | Gene or genomic region |
| LRG | Locus Reference Genomic sequence: Gene or genomic region, used in a diagnostic setting |
| NM | Protein-coding RNA (mRNA) |
| NR | Non-protein-coding RNA |
| NP | Protein (amino acid) sequence |
The variant description begins by depicting the type of reference sequence used (c = coding DNA sequence, g = genomic reference sequence). When a protein-coding reference sequence is used (c), the nucleotide numbering begins with a 1, which represents the first position in the protein-coding region (the A of the translation-initiating ATG), and ends at the last position of the stop codon. Thus, if you divide the position number by 3, you can identify the affected amino acid in the protein sequence e.g., using the same example as above, 4375/3 = 1459, indicating that the predicted consequence affects amino acid 1459, which is an arginine. Different variants are indicated using different notations (explained in Table 2).
Table 2. HGVS notation and examples for the most common types of mutations2
| Notation | Example | Explanation |
| > | c.4375C>T | Substitution of the C nucleotide at position c.4375 with a T |
| del | c.4375_4379del or c.4375_4379delCGATT | Nucleotides from position c.4375 to c.4379 deleted |
| dup | c.4375_4385dup or c.4375_4385dupCGATTATTCCA | Nucleotides from position c.4375 to c.4385 duplicated |
| ins | c.4375_4376insACCT | ACCT inserted between positions c.4375 and c.4376 |
| delins | c.4375_4376delinsACTT or c.4375_4376delCGinsAGTT | Nucleotides from position c.4375 to c.4376 (CG) are deleted and replaced by ACTT |
When only DNA has been analyzed, the RNA- and protein-level consequences of the variant can only be predicted, and should thus be reported in parentheses e.g., p.(Arg1459*) is the predicted effect at protein level (p) for the example described above.
For all variant descriptions using HGVS nomenclature, the nucleotide at the most 3’ position of the variation in the reference sequence is arbitrarily assigned to have changed (see how to apply this rule in Figure 2).4 The exception is for deletions/duplications around exon junctions for which shifting the variant 3’ would place it in the next exon.5
Although the HGVS recommendations can be difficult to understand and might take a bit of getting used to, if you break them down and refer to the examples in this guide, you are on the road to success!
If you want to accelerate your variant annotation and interpretation, Alamut™ Visual Plus is a comprehensive, full genome browser for efficient and user-friendly variant interpretation. The software accelerates the complex and time-consuming assessment of variants thanks to its user-friendly interface and integrated features for variant annotation and analysis.
Find out how Alamut™ Visual Plus applies the HGVS nomenclature recommendations to ensure that variant annotation follows the universally applied standards for variant analysis, interpretation, and reporting in our dedicated Technical Note.
Alamut™️ Visual Plus is for Research Use Only. Not for use in diagnostic procedures.
References
Dr. Mohamed Z Alimohamed kindly summarized his upcoming peer-reviewed publication in Gene:
“Current splice prediction algorithms have limited sensitivity and specificity, therefore many potential splice variants are classified as variants of uncertain significance (VUSs).
However, functional assessment of VUSs to test splicing is labor-intensive and time-consuming. We have developed a decision tree, SEPT-GD, by setting thresholds for the splice prediction programs implemented in Alamut™️ to prioritize potential splice variants associated with cardiomyopathies for functional studies, and functionally verified the outcome of the decision tree.
SEPT-GD outperforms the tools commonly used for RNA splicing prediction and improves prioritization of variants in cardiomyopathy genes for functional splicing analysis.”
Click here to read the full publication.
Alimohamed MZ, Boven LG, van Dijk KK, Vos YJ, Hoedemaekers YM, van der Zwaag PA, Sijmons RH, Jongbloed JDH, Sikkema-Raddatz B, Westers H. SEPT-GD: A decision tree to prioritise potential RNA splice variants in cardiomyopathy genes for functional splicing assays in diagnostics. Gene. 2023 Jan 30;851:146984.
Alamut™️ is for Research Use Only. Not for use in diagnostic procedures.
Discover what makes SOPHiA DDM™ effective at calling mtDNA variants from exome sequencing data, and see for yourself how in a single workflow, the SOPHiA DDM™ Platform complemented by Alamut™ Visual Plus can be used to identify and interpret variants in mtDNA alongside SNVs, Indels, and CNVs in nuclear DNA.
Our Technical Note outlines the guidelines and standards behind the nomenclature convention deployed in Alamut™ Visual Plus. We also explain how Alamut™ Visual Plus applies them to ensure that variant annotation follows the universally applied standards for variant analysis.
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At the American Society of Human Genetics (ASHG) Annual Meeting this year, our esteemed speakers shared the ins and outs of how the SOPHiA DDM™ Platform, in combination with Alamut™ Visual Plus, adapted to their laboratories’ needs to provide sample-to-report workflows that streamlined the identification and interpretation of nuclear and mitochondrial variants associated with rare and inherited diseases, including hereditary cancers.
All SOPHiA GENETICS™️ products discussed in this article are for Research Use Only – not for use in diagnostic procedures. SOPHiA GENETICS™ does not facilitate and does not accept any liability for any validation of SOPHiA GENETICS™ products for clinical use by a third party.
Exome sequencing with combined mitochondrial genome sequencing for the detection of nuclear and mitochondrial DNA variants
Jessica Van Ziffle, PhD, FACMG Associate Clinical Professor, Pathology at University of California, San Francisco, California, United States
In the Pathology laboratory at the University of California, the proportion of positive/probably positive variants detected in pediatric and prenatal cases analyzed using the SOPHiA DDM™ Custom Whole Exome Solution (optimized for the Illumina NovaSeq 6000) was consistent with the literature (see charts). Approximately 70% of the positive pediatric cases were associated with autosomal dominant inheritance. Most reported variants were missense single nucleotide variants (SNVs), with the positive cases fairly equally split between frameshift, nonsense, and missense variants.
Proportion of positive/probably positive findings for pediatric and prenatal exome cases
Figure sourced from Jessica Van Ziffle’s presentation
With the goal of increasing the proportion of positive findings, Jessica and the team at UCSF explored what additional variants could be identified by exome sequencing to potentially solve the ∼10% of inconclusive cases and ∼65% of negative cases. First, the team investigated the impact of calling copy number variants (CNVs), specifically contiguous gene changes, whole gene changes, and exon-level changes. UCSF worked closely with SOPHiA GENETICS™ to optimize their exome sequencing to ensure high and even coverage for accurate CNV detection, and indeed doubled their sequencing depth to 80M reads to ensure the sensitive detection of CNVs 1-2 exons in size.
Next, UCSF wanted to be able to simultaneously call variants in mitochondrial DNA, which is especially relevant for metabolic diseases. Different cell types have different numbers of mitochondria, and each mitochondrion has its own genome that can have different variants in it (heteroplasmy). The UCSF team, therefore, wanted to assess the lower limit of detection for mitochondrial heteroplasmy through a mixing study, which concluded that exome testing could detect variants down to 5% variant allele fraction with high sensitivity.
Streamlining clinical implementation of hereditary cancer analysis and reporting with a custom application
Hong Wang, PhD, FCCMG, FACMG, DABMGG Laboratory Geneticist at North York General Hospital, Toronto, Ontario, Canada
Andrea Vaags, PhD, FCCMG Discipline Co-Lead and Laboratory Geneticist at Trillium Health Partners – Credit Valley Hospital, Mississauga, Ontario, Canada
Drs Wang and Vaags provided a step-by-step overview of how they developed a brand new hereditary cancer panel to meet the Ontario Health - Cancer Care Ontario criteria for hereditary cancer testing.
Laboratory and clinical working groups were established to evaluate evidence and identify key genes and non-coding variants to include in a cutting-edge custom hereditary cancer panel. Furthermore, genetic testing eligibility criteria were co-developed with the Hereditary Cancer Clinical Eligibility Working Group. The laboratory working group used an evidence-based framework to design a standardized 76-gene panel, organized into 13 larger disease site-linked panels, and 25 single/small gene panels. After designing the panel, the Ontario group worked with SOPHiA GENETICS™ to expeditiously develop and implement the custom SOPHiA DDMTM Hereditary Cancer application in academic community hospitals (see timeline).
Timeline of SOPHiA DDM™ Hereditary Cancer panel implementation in Ontario hospitals
Figure sourced from the Ontario hospital responsible for validating this product
Thanks to the streamlined end-to-end SOPHiA GENETICS™ workflow, hereditary cancer testing approximately doubled, according to Dr Vaags.
The workflow for each batch of 70 samples (plus one control) in the Ontario group laboratories, consists of DNA preparation, automated 3-day library preparation using the SOPHiA GENETICS program on the Hamilton STARlet, and sequencing on a NextSeq® 550 using mid-output. Sequencing data are automatically uploaded to the SOPHiA DDM™ cloud for processing ahead of analysis. For additional time savings, genes requiring special consideration due to the presence of pseudogenes are flagged with a warning in the SOPHiA DDM™ Platform and the SOPHiA GENETICS™ support team is on hand to answer queries on unusual findings. The cloud-based software for data management enables the laboratories to streamline data access, storage, and archiving back-up. Dr Wang shared that the time saved through this workflow has been instrumental in maintaining turnaround times, especially with significant understaffing during challenging periods.
By applying Virtual Panels and custom filters, the teams can analyze from as little as a single variant to as many as 76 genes using a single workflow. The high analytical sensitivity and specificity enable the laboratories to pick up unusual findings, such as Alu insertions, Boland inversions, and low-level mosaicism of copy number changes. And finally, the one-step secondary and tertiary analysis for concurrent detection of SNVs and CNVs allows the teams to significantly speed up their analysis, and the pseudogene pipeline enables the laboratories to minimize reflex testing. In summary, the custom SOPHiA DDM™ Hereditary Cancer application provides the Ontario laboratories with a one-size-fits-all solution.
Screening for genetic variants in hereditary cancer syndromes using the end-to-end SOPHiA DDM™ workflow
Mark Williams, FHGSA – Chief Scientist at Genomic Diagnostics, Heidelberg, Victoria, Australia
Speaker Mark Williams began his talk by highlighting that a key goal of the Genomic Diagnostics lab is to facilitate equal access to hereditary cancer testing. To do this, the lab set multiple criteria that were highly important to them when developing a new hereditary cancer application. Employing the complete SOPHiA GENETICS™ workflow for Hereditary Cancer allowed the team at Genomic Diagnostics to successfully meet these testing criteria.
In collaboration with Genomic Diagnostics, the custom SOPHiA DDM™ Hereditary Cancer application was designed to include genes that align with current practice guidelines. It was important to the lab that the pipeline could detect SNVs, Indels, and copy number variations (CNVs) in a single workflow. Mark confirmed that the resultant application effectively detects CNVs and is scalable, with turnaround times that meet their needs, even with testing volumes increasing year-on-year. In addition, the solution provides high-quality, consistent results, a full record of curation, visualization of BAM files, and is easily accessible and usable by all laboratory staff.
Like numerous other SOPHiA GENETICS™️ customers, Mark concluded that the SOPHiA DDM™ Platform offers a robust, automated, and secure bioinformatics pipeline that meets Australia’s privacy regulations. In addition, the software is extremely user-friendly, from its visual interface to the detailed QC metrics, annotation information, and links to databases. All laboratory personnel can effectively use the end-to-end solution, even without prior bioinformatics expertise.
The integrated workflow and affordable price allowed Genomic Diagnostics to expand access to the custom SOPHiA DDM™ Hereditary Cancer application (see chart), meeting Genomic Diagnostics’ goal of facilitating equal access to hereditary cancer testing.
Increasing access to hereditary cancer genomic testing over time
Figure sourced from Mark Williams’ presentation
We thank all our speakers for sharing their research stories at our ASHG symposium this year. We’re delighted to hear how their integrated SOPHiA DDM™ workflows are reducing workloads, expanding access, and continuing to discover new variants associated with rare diseases and hereditary cancers.
SOPHiA GENETICS products are for Research Use Only and not for use in diagnostic procedures unless specified otherwise.
SOPHiA DDM™ Dx Hereditary Cancer Solution, SOPHiA DDM™ Dx RNAtarget Oncology Solution and SOPHiA DDM™ Dx Homologous Recombination Deficiency Solution are available as CE-IVD products for In Vitro Diagnostic Use in the European Economic Area (EEA), the United Kingdom and Switzerland. SOPHiA DDM™ Dx Myeloid Solution and SOPHiA DDM™ Dx Solid Tumor Solution are available as CE-IVD products for In Vitro Diagnostic Use in the EEA, the United Kingdom, Switzerland, and Israel. Information about products that may or may not be available in different countries and if applicable, may or may not have received approval or market clearance by a governmental regulatory body for different indications for use. Please contact us to obtain the appropriate product information for your country of residence.
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