Dear All, Greetings from a showery East Anglia. In this update: - DECIPHER v11.5 Released o G2P eye, skin and cancer panels o Genes tables: GenCC gene-disease validity data and table filters o Protein view for patient copy-number variants o Further transcript details on protein view o Genome browser reverse strand track o LOEUF score colouring by constrained deciles DECIPHER v11.5 Released ============= You can also view this on the web at: https://www.deciphergenomics.org/about/news Gene2Phenotype eye, skin and cancer panel information is now displayed in DECIPHER, in addition to the developmental disorder panel data. This is displayed around the website, including on gene pages, as shown here for PTEN: https://www.deciphergenomics.org/gene/PTEN/overview/clinical-info GenCC gene-disease validity data is now displayed in the genes table. GenCC brings together groups engaged in the evaluation of gene-disease validity to facilitate the consistent assessment of genes that have been reported in association with disease. The classification and number of submitters supporting that classification is displayed in the genes table. Further information is displayed by clicking on the classification. In addition, new filters are available on genes tables, including "Disease-associated" and "Monoallelic genes". These filters can be used to view genes relevant to the patient. Information about the filters can be viewed by clicking on the information icon next to the filter. These new features can be seen for a patient with a likely pathogenic deletion here: https://www.deciphergenomics.org/patient/284613/genotype/58320/genes To aid in the interpretation of copy-number variants, patient genes tables now detail how much a copy-number variant overlaps each gene. In addition, breakpoints are displayed on the protein browser to allow users to determine which region of the protein is deleted/duplicated. In this example, the patients' deletion partially overlaps POLR1A (39.99 kb of coding region), and the protein browser at the bottom of the page shows that exons 14 to 34 are deleted: https://www.deciphergenomics.org/patient/277626/genotype/51511/genes/POLR1A…. In a similar way, intragenic copy-number variants are shown on the protein browser. In this example exons 22 to 25 of SCN2A are deleted: https://www.deciphergenomics.org/patient/271955/genotype/104440/genes/SCN2A…. Codon phase (position of an exon/intron boundary within a codon) can be determined by clicking on the relevant exon: where the start phase and end phase differs, such variants will cause a frameshift. The transcript used in the protein view is now displayed, along with information about the number of exons and the amino acid length. If the depositing centre have chosen a different relevant transcript, this transcript is listed along with transcript information. In this example, it can be seen that for the two transcripts, the protein coding sequence is identical: https://www.deciphergenomics.org/patient/341344/genotype/202211/protein To assist in the interpretation of variants in genes on the reverse strand, the reverse and forward strand sequence is now shown in the genome browser. The alt and ref reverse strand sequence are also shown in the patient genotype table. This can be seen for a patient with a SCN3A variant here: https://www.deciphergenomics.org/patient/258829/genotype/197751/browser The colouring of LOEUF scores has been updated so that the colouring now represents constrained deciles as detailed in Karczewski et al., 2020 (https://europepmc.org/article/MED/32461654). Genes in the most constrained decile (which have a LOEUF score of 0.268 or below) are coloured red. ============= We look forward to your feedback and suggestions for improvement. Please use the "Feedback" button which is available on every page and fill in the simple form to get in touch with us. Your details will be filled in automatically if you are logged in. Best Regards Julia, on behalf of the DECIPHER team Julia Foreman PhD DECIPHER Project Manager Email: contact(a)deciphergenomics.org Web: https://www.deciphergenomics.org Twitter: @decipher_wtsi