Current product limitations¶
The New IB is an evolving product, undergoing continuous development and improvement (as per best-practice) based on user feedback and emerging service requirements. Initial focus was placed on supporting the end-to-end interpretation of small variants. The remaining functionality, required for end-to-end interpretation of all GMS cases is therefore not yet available, but is earmarked for future releases (you can check our roadmap and tell us what is important to you).
Existing limitations of the New IB are listed below:
| Limitation | Affects version | Impact | Workaround |
|---|---|---|---|
| GMS cases with tiered CNVs and/or tiered STRs (including Tier Nulls) cannot yet be analysed in the New IB, as these variant types are not yet supported. This represents ~82% of GMS cases, for reference. | v4.0.0 | These cases will not have an active (blue) New Interpretation Browser button in the Interpretation Portal, to indicate that you can’t open them in the New IB for analysis. Only a small proportion of GMS cases (~18%) can currently be analysed in the New IB. |
Continue to analyse cases with tiered CNVs and/or tiered STRs via existing products. Same is true for reporting of any Tier Null STRs, which requires analysis via the Interpretation Portal. Support for CNVs and STRs is in our roadmap, with CNV development already underway. |
| Case-level information (e.g. panel coverage, BAF plots, Summary of Findings) and raw sequencing files (VCFs) for the case are not yet supported in the New IB. | v4.0.0 | You won't be able to see the gene panel coverage data, BAF plots and download VCFs for the case in the New IB | Continue to use the Interpretation Portal to review coverage and BAF data, or download raw sequencing files. |
| No ability to record specific ACMG criteria to save evidence as part of interpretation | v4.0.0 | Sub-optimal experience, increasing interpretation time. | Use the variant comment box to type in and save all the evidence behind your interpretation. We are already working on supporting ACMG criteria. |
| No variant filtering capability and preset filters in place. | v4.0.0 | No impact in cases with a small number of mandated variants for review. In cases with too many Tiered (1/2/3), De-novo or Incomplete Penetrance variants, the absence of filters can impact analysis efficiency. The same is true when looking for variants on specific genes (e.g. following a clinician request), due to the sheer number of variants available (full genome). |
When a diagnosis is not immediately found in the core set of variants (Tier 1, Tier 2, Exomiser rank 1-3) and the case requires analysis of all De novo variants, Incomplete Penetrance variants or lookup of specific genes, those checks are better suited for existing products. Filters and presets are already in our roadmap, for a future iteration. We recognise the need to support all use cases. |
| Basic support for Compound Heterozygous (CompHets) variants | v4.0.0 | You will still be able to see what variants are CompHets, but improvements are required for greater efficiency. | Use the Segregation, inheritance and penetrance column, which will be showing CompHet for such variants. Improvements to CompHets are in our roadmap. This will become more important when we support CNVs and STRs. |
| Variant segregation and inheritance annotations are only available for variants considered by Tiering and Exomiser. | v4.0.0 | The Segregation, inheritance and penetrance column will be empty for variants that were not part of the Interpreted Genome. | Use the zygosity columns and IGV to infer inheritance, if you are reviewing a variant outside the core set of variants mandated for review. |
| No export function (e.g. CSV/PDF) available for bulk variant data | v4.0.0 | No ability to export list of variants interpreted in case, to save in local system | A printscreen of the reporting page can serve as a record of all the variants that were interpreted in the case, or you can save the Summary of Findings PDF that is available for the case in the Portal. This is in our roadmap but is not yet a high priority – tell us if it is important to you. |
| Explanation for non-PASS variant status is not provided | v4.0.0 | You will be able to see that a variant is non-PASS, with the Dragen QC filter shown, but you won’t know why it failed QC | Consult the Dragen user guide to understand what the QC status refers to, if you’re reviewing any non-PASS SNV. This is not yet in our roadmap, but tell us if it is important to you. |
| Case list and email notification for ready cases in the New IB, is not yet available | v4.0.0 | You won’t see a list of cases in the New IB, and can only open up specific cases, via the Interpretation Portal. | Start your interpretation journey by selecting cases to analyse via the Interpretation Portal. The case list will be ported over from IP into the New IB at a future stage (undefined currently). We will engage with you to understand you needs when the time comes. |
The above limitations are included in the Clinical Safety Case Report for the New IB, Hazard Log (DCB 0129) and our internal Risk Registry. All documents are available upon request.
The New IB is currently available alongside the existing RD Interpretation products and workflows; these remain unchanged for the time being. Existing systems can therefore still be used as pathway for analysis or used as failsafe.
Abbreviations
| Abbreviation | Definition |
|---|---|
| ACGS | Association for Clinical Genomic Science |
| ACMG | American College of Medical Genetics and Genomics |
| CDS | Coding DNA Sequence |
| CNV | Copy Number Variant |
| CVA | Clinical Variant Ark |
| New IB | New Interpretation Browser |
| GEL | Genomics England |
| GMS | Genomic Medicine Service |
| GLH | Genomic Laboratory Hub |
| HGVS | Human Genome Variation Society |
| HTML | Hyper Text Markup Language |
| HSCN | Health and Social Care Network (N3) |
| IGV | Integrative Genomics Viewer |
| IP | Interpretation Portal |
| NGIS | National Genomics Informatics System |
| PID | Patient Identifiable Data |
| QC | Quality Control |
| SO | Sequence Ontology |
| SNV | Single Nucleotide Variant |
| SV | Structural Variant |
| TOMS | Test Order Management Service |
| UAT | User Acceptance Testing |
| VCF | Variant Call Format File |
| WGS | Whole Genome Sequencing |