Table 1.

Gene disease validity classification

Definitive

• Role has been repeatedly demonstrated in research and clinical diagnostic settings

• Upheld over time (in general, at least 3 years)

• No convincing contradictory evidence

Strong

At least 2 separate studies with the following:

• Numerous unrelated probands harboring variants with evidence for causality

• Typically, experimental evidence is also present (but not required)

• No convincing contradictory evidence

Moderate

≥1 independent study with the following:

• Several unrelated probands with pathogenic variant

• Some supporting experimental data

• No convincing contradictory evidence

Limited

≥1 independent study with the following:

• <3 unrelated probands with pathogenic variants OR

• Multiple variants reported in unrelated probands but without sufficient evidence for pathogenicity

• No convincing contradictory evidence

Gene-Disease Validity Classification levels and their descriptions, as per the Standard Operating Procedures Document for Gene-Disease Validity (May 2022 https://www.clinicalgenome.org/site/assets/files/5391/version_9_gene_curation_sop_final2.pdf). Genes that have previously been curated for neurodevelopmental disorder assertions with “Moderate” or “Limited” levels of evidence are given the highest priority for BGR gene selection.