Structural variants

Structural variants (SVs) are larger rearrangements, deletions, insertions, duplications, inversions, and translocations, typically ≥ 50 bp. Long-read sequencing resolves many SVs that short reads miss, especially in repetitive regions. Copy-number variants are reviewed on their own tab; see Copy number.

Visualizations

The Structural Variants tab adds visualizations to make review easier:

• Track & histogram view: the variants laid out along the genome, colour-coded by type.

• Circos plot: shows the relationships between variants across the genome (for example, the two ends of a translocation).

The candidate list

Alongside the visualizations, the variant list shows the SV calls. You can search, sort, filter, and customize the columns in the table using the Columns dropdown.

The default columns in the candidate table include:

Column	Description
User Classification	The classification manually assigned to the structural variant by a reviewer (e.g., Pathogenic, Likely Pathogenic, VUS, Benign).
Automated Classification	The automated classification generated by the system's pipeline rules or algorithms.
Chrom	The chromosome where the structural variant is located.
Pos	The starting genomic coordinate (position) of the structural variant.
SV Type	The type of structural variant (e.g., DEL (deletion), INS (insertion), DUP (duplication), INV (inversion), BND (breakend/translocation)).
SV Length	The length of the structural variant in base pairs.
Genes	Standard gene symbols of the genes overlapped or affected by the structural variant.
HiFi Solves AF	The allele frequency of the structural variant in the HiFi Solves reference database.
gnomAD Allele Frequency	The allele frequency of the structural variant in the gnomAD SV database.
Pathogenicity Score	A composite pathogenicity score calculated for the structural variant.
Exomiser Score	The score computed by Exomiser assessing the potential pathogenicity and phenotypic relevance of the variant.
PhenoGenius	The pathogenicity score computed by PhenoGenius based on phenotypic relevance and genomic annotations.
AnnotSV Score	The annotation/pathogenicity score or class assigned by AnnotSV.
StrVCTVRE Score	The score computed by StrVCTVRE, assessing pathogenicity of structural variants affecting exons.
Genotype	The zygosity and phase of the structural variant in the sample.

Selecting a variant opens its detail view, where you can inspect the call, explore the affected gene, open IGV, and classify the variant to add it to the report.

Filters

The filter drawer offers:

• User Classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign.

• Automated Classification: the pipeline's ACMG classification. This tab opens pre-filtered to Pathogenic and Likely Pathogenic.

• Gene: filter by gene symbol.

• SV Type: DEL, INS, DUP, BND, INV.

• Chromosome: chr1 to chr22, chrX, chrY.

• Position: a genomic-coordinate range.

How to review

1. Use the track/histogram and circos views to orient on the events and their genomic context.

2. Focus on rare events overlapping phenotype-relevant genes.

3. For each candidate, review type, size, and overlapping genes in the detail view.

4. Classify and add findings to the report.

SVs are evaluated by which genes and regions they overlap, not by a single position. Two events of the same type can differ greatly in significance depending on exactly which exons they intersect.