Connected variants tab

The Connected Variants feature in Emedgene helps geneticists identify and interpret relationships between variants within the same case. This functionality is especially important when working with data from DRAGEN and its MRJD (Multi Region Joint Detection) caller, which improves variant calling in hard-to-map regions of the genome.

Available for both VCF and FASTQ input files.

Ambiguous calling and JIDS

Some MRJD caller variants are ambiguously placed because they could belong to more than one location in the genome.

• These are linked together by a Joined ID (JIDS).

• Emedgene displays these as "Ambiguous calling" and allows filtering via the Calling Methodology filter.

Warning: Variants with JIDS should be reviewed carefully since their genomic placement is uncertain.

The Connected Variants component

• On the Variant Page between the Population Statistics and Related Cases tabs.

• In the Summary tab.

It displays three types of variant relationships:

1. MNVs → Multi-nucleotide variants occurring within 2 nucleotides.

2. Ambiguously called variants → From DRAGEN MRJD, linked by JIDS.

3. Compound Heterozygotes → Only shown in trio cases (child + both parents) where variants are inherited from different parents.

Modes:

• Simple Mode → Shows all connected variants.

• Advanced Mode → Allows filtering by any of the 3 connection types.

Supported Variant Types: SNVs, Indels, SVs, CNVs, mtDNA, and STRs.

Warnings:

• Only the first 50 connected variants are displayed.

• Always confirm variant interpretation for JIDS-linked variants, as they may represent mapping ambiguities.

• For compound heterozygotes, ensure parental confirmation is available to validate in-trans status.

Tips:

• Use Advanced Mode for targeted review when you want to focus on specific relationships like compound heterozygosity.

• Use Calling Methodology filters to quickly isolate ambiguous variants for review.

• In trio cases, connected variants can reveal inheritance patterns that are critical for classification.