Candidates tab

The Candidates tab displays all tagged variants, whether tagged by the AI Shortlist or manually by a user.

Variant tagging by the AI Shortlist

Variants are automatically tagged as:

• Most Likely Candidates and Candidates

  Variants prioritized by the AI Shortlist

• Secondary findings

  Variants that meet ACMG-defined criteria for secondary findings and automatically tagged with an Incidental tag (if enabled)

• Carrier variants

  Variants identified by the carrier analysis pipeline (if enabled)

Assigning variant tags during review

During review in the Candidates tab, additional tags can be applied to a variant alongside the original automatic tag.

The Candidates tab presents:

Most Likely Candidates and Candidates

A set of the most promising variants based on scores calculated by the AI Shortlist. These variants are initially tagged by the system.

Variant types assessed:

• SNVs and indels

• CNVs

• SVs

• mtDNA variants

• STRs

Incidental (Secondary)*

Secondary findings are variants that are automatically assigned the Incidental tag when they meet the criteria for secondary findings as defined by the American College of Medical Genetics and Genomics (ACMG).

Tagging is applied only when the Secondary findings checkbox is selected during case creation.

Tagging criteria

A variant is automatically tagged as an incidental (secondary) finding if it meets all of the following criteria:

1. Classification: Previously classified as pathogenic or likely pathogenic in ClinVar or Curate variant databases

2. Zygosity: Heterozygous or homozygous (only homozygous for the HFE gene)

3. Allele frequency: Less than 5%

4. Read depth: 10× or higher

5. Variant quality: Any value but LOW

6. Affected gene: Listed in the ACMG SF v3.2 medically actionable gene list for reporting secondary findings in clinical exome and genome sequencing (PMID: 37347242)

ACMG SF v3.2 gene list

ACTA2, ACTC1, ACVRL1, APC, APOB, ATP7B, BAG3, BMPR1A, BRCA1, BRCA2, BTD, CACNA1S, CALM1, CALM2, CALM3, CASQ2, COL3A1, DES, DSC2, DSG2, DSP, ENG, FBN1, FLNC, GAA, GLA, HFE, HNF1A, KCNH2, KCNQ1, LDLR, LMNA, MAX, MEN1, MLH1, MSH2, MSH6, MUTYH, MYBPC3, MYH11, MYH7, MYL2, MYL3, NF2, OTC, PALB2, PCSK9, PKP2, PMS2, PRKAG2, PTEN, RB1, RBM20, RET, RPE65, RYR1, RYR2, SCN5A, SDHAF2, SDHB, SDHC, SDHD, SMAD3, SMAD4, STK11, TGFBR1, TGFBR2, TMEM127, TMEM43, TNNC1, TNNI3, TNNT2, TP53, TPM1, TRDN, TSC1, TSC2, TTN, TTR, VHL, WT1.

*In Emedgene, the terms "incidental findings" and "secondary findings" both refer to secondary findings as defined by the ACMG, due to historical usage.

When Emedgene was first released, the term “incidental findings” was adopted in alignment with the clinical genomics standard at the time. The 2013 ACMG recommendations defined incidental findings as “the results of a deliberate search for pathogenic or likely pathogenic alterations in genes that are not apparently relevant to a diagnostic indication for which the sequencing test was ordered” (PMID: 23788249).

As the field evolved, the ACMG and broader clinical community began to distinguish between “incidental findings” (unexpected, not actively sought) and “secondary findings” (intentionally analyzed and reportable). This shift was reflected in the updated 2016 ACMG guidance (PMID: 27854360).

To reflect this change, Emedgene introduced the term “secondary findings” into the platform. However, “incidental findings” remains in use throughout the platform for technical consistency.

Carrier

Variants identified by the Carrier analysis pipeline. Carrier variants are automatically tagged only if you've selected the Carrier Analysis checkbox while creating a case. Analysis requirements and a list of targeted regions are specified by the organization's manager. This Carrier analysis flow is implemented by request.

In Report and other custom variant tags

Variants that were manually selected to be reported.