Haplotype phase (cis/trans)

For autosomal recessive conditions, a phenotype usually appears only when both copies of a gene are affected:

• Homozygous: the same variant on both copies of the gene.

• Compound heterozygous: two different variants, one on each copy (in trans).

Two heterozygous variants on the same copy (in cis) leave the other copy intact, which usually rules out a recessive explanation. When the sample's calls are phased, the Variant Interpreter shows which of these applies. Phase appears in two places: on each variant, and summarized for the whole case on the Summary tab.

The Haplotype phase panel

The Haplotype phase panel sits at the top of the variant drawer for every variant type except methylation. Its header names the gene and how many of the gene's calls are shown.

Gene status

A status chip describes how well the gene is phased in this sample:

Status	Meaning
Phase resolved	The gene's calls fall in a single phase set, so pairs can be placed on haplotypes.
Block switch	The gene spans two or more phase sets. Calls in different sets can't be placed relative to each other, so trans can't be claimed.
No phase information	None of the gene's calls are phased.
Not assessable	The gene has no heterozygous calls to phase.
Not fully counted	Not all of the gene's calls could be counted. Counts read "At least N".

If no phase information was ingested for the sample at all, the panel says so and no chip is shown.

Diagram

The diagram draws the gene's calls on Haplotype 1 and Haplotype 2 tracks, one block per phase set, with a visible break between phase sets. Unphased heterozygous calls are drawn off the tracks with a dashed outline. Homozygous calls sit on neither track.

Verdicts

Below the diagram, one row compares this variant with each other small variant in the gene:

Verdict	What it means
In trans — compound heterozygous	The two variants are on opposite haplotypes.
In cis — same haplotype	The two variants are on the same haplotype.
Phase unresolved	The pair can't be placed. The reason is shown, for example the calls are in different phase sets, or one call is unphased.
Homozygous — phase does not apply	One variant is homozygous, so phase isn't needed.
Multi-allelic — not assessed here	The site is multi-allelic and isn't assessed.

An evidence row shows the gene's Het calls, how many are Phased, and the number of Phase sets.

An In cis verdict can rule out a compound heterozygous explanation. Confirm it before acting on it. When a pair is Phase unresolved, trans can't be claimed from phasing alone: inspect the haplotype-tagged reads in the genome browser, or confirm by parental segregation.

How to review a pair

1. Open a small variant in a gene with another candidate variant.

2. Check the gene status chip. Phase resolved means phasing can place the pair on haplotypes; Block switch or No phase information means it can't.

3. Read the verdict for each pair.

4. If a pair can't be placed, click Verify in the genome browser to open the genome browser and inspect the reads by haplotype.

5. Evaluate each variant on its own evidence (frequency, consequence, clinical annotation), then assess the pair together.

6. Classify the variants and record the phase in your interpretation.

The Haplotype phase card on the Summary tab

The Summary tab carries a Haplotype phase card that applies the same assessment to every gene where the priority findings include two or more small variants. It shows:

• how many priority-finding pairs have a phase verdict;

• a badge reading All reported pairs callable, or how many genes are not callable in trans;

• a bar showing how the genes break down by phase status;

• two worklists, Pairs with a phase verdict and Not callable in trans, with links that open each variant.

Use the Not callable in trans list to find the pairs that need browser review or parental testing before you report a compound heterozygote.

Phase is assessed on the proband's calls. In a trio, the parents' calls are not counted towards the proband's phase verdicts.