PanelApp criteria for diagnostic grade 'green' genes

One of the three criteria A, B or C below must be met.

Criterion A

There are plausible disease-causing mutations¹ within, affecting or encompassing an interpretable functional region of this gene² or identified in multiple (>3) unrelated cases/families with the phenotype³.

Criterion B

There are plausible disease-causing mutations¹ within, affecting or encompassing cis-regulatory elements convincingly affecting the expression of a single gene identified in multiple (>3) unrelated cases/families with the phenotype³.

Criterion C

As Critera A or B but in 2 or 3 unrelated cases/families with the phenotype, with the addition of convincing bioinformatic or functional evidence of causation e.g., known inborn error of metabolism with mutation in orthologous gene which is known to have the relevant deficient enzymatic activity in other species; existence of an animal model which recapitulates the human phenotype.

Both criteria D and E must be met.

Criterion D

Evidence indicates that disease-causing mutations follow a Mendelian pattern of causation appropriate for reporting in a diagnostic setting⁴.

Criterion E

No convincing evidence exists or has emerged that contradicts the role of the gene in the specified phenotype.

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1. Plausible disease-causing mutations: Recurrent de novo mutations convincingly affecting gene function. Rare, fully-penetrant mutations - relevant genotype never, or very rarely, seen in controls. ↩↩

2. Interpretable functional region: ORF in protein coding genes miRNA stem or loop. ↩

3. Phenotype: the rare disease category, as described in the eligibility statement. ↩↩

4. Intermediate penetrance genes should not be included. ↩