Internal inclusion list

Internal inclusion lists are static lists that were compiled by Genomics England clinical and curation teams, with the input of external specialists. Currently, all variants in the internal inclusion list are required to have PubMed ID as the evidence source.

They are being used for two reasons:

• For genes, where other databases (ClinVar and CVA) contain a large number of pathogenic and likely pathogenic variants not suitable for reporting in the newborn screening context. This could be due to several reasons, e.g. gene associated with multiple conditions or multiple modes of pathogenicity, not all of which are being screened for, or containing variants with mild or low penetrance phenotypes. In such cases, the genes are tagged as “Internal inclusion list only” in PanelApp and variants from ClinVar and CVA are not prioritised in those genes. LOF prioritisation may still be applied for these genes, if appropriate, for the mechanism of disease.
• Internal inclusion lists can also be used to supplement other variant lists, if other sources are missing important clinically relevant variants.

To be considered in prioritisation, a variant needs to match a variant on the internal inclusion list OR cause the same predicted protein change as a variant on the internal inclusion list.

Further information on the variants in the internal inclusion lists can be obtained on request from Genomics England, or from the internal inclusion lists page (accessible for Genomics England employees only).