Variant summary display

In both the Shortlist tabs and Filter view, each variant is listed with a summary display, grouping the most crucial annotations. To explore more detailed annotations on the variant, the Variant card can be opened.

SNV summary annotations

The following annotations and links are provided in the variant summary display of the SNV/Carrier results and in the filter view:

Gene name (according to HGNC): The menu next to the gene name links to public sources OMIM, PubMed, NCBI genes, HUGO genes, Uniprot and MGI.

Chromosomal location of the variant with links to Ensembl, UCSC, DECIPHER, Mitomap (for mitochondrial variants), Google Scholar, Alamut Visual genome browsers and to IGV. To open variants in either Alamut Visual or IGV, these applications should be opened on your computer and, in case of IGV, the BAM file of the sample of interest should be opened. When clicking the Alamut or IGV links in Moon, these programs will jump to the location of the Moon variant.

rsID of the variant (if available)

ClinVar label if the variant is listed on ClinVar. Clicking the label will open a new tab with the ClinVar page of the variant in question.

Invitae label if the variant is included in Invitae’s internal knowledge base (InvitaeKB).

KB label if the variant is listed on your lab's knowledge base. Clicking the label will redirect you to the KB page of the variant in question, allowing you to review the annotations provided in the KB.

Genotype: The genotype is shown as the combination of Ref and Alt alleles based on the exact genotype call in the VCF (0/1 or 1/1). In the displayed genotype, the reference allele is colored black whereas the alternate allele is colored red. The reference allele is also displayed as such below the genotype. For X-linked calls in males, all variants in the VCF with either 0/1 or 1/1 genotypes, are indicated as hemizygous alternate calls, and considered as such for the analysis.

Predicted effect of the variant (eg. missense, stop gained, frameshift, intronic…).

Protein notation for coding variants (HGVS)

Coding notation: In the overview table, you can switch between protein and coding notation by clicking on it.

Publications: Link to Mastermind (by Genomenon), an extended database of scientific literature. If a specific c. and/or p. notation has ever appeared in scientific literature, the number of publications mentioning the variant in Mastermind is listed. The link redirects the user to Mastermind, where further assessment of the publications can be made.

Disorder name with link to OMIM/PubMed (annotated based on Apollo). For genes linked to more than one disease phenotype, Moon annotates the best disease match based on concordance between the genotype of the patient and the disease’s known inheritance pattern, and phenotypic overlap with the inputted clinical features.

Inheritance pattern of the suggested disease as present in Apollo (eg. AR, AD, XR, XD, MT)

Segregation information in case of a family analysis (de novo, compound heterozygous)

Indication of how many comments have been added to the variant in the current or other cases.

In the Filter view, it is indicated for each variant why the variant was filtered out of the analysis of the automated pipeline. For variants in the shortlist, this field indicates the variant to be shortlisted by Moon.

Warning icons might be shown in the overview table, indicating that some of the annotations are not as expected. Details on these warnings are provided in the variant cards.

SV/CNV summary annotations

Summary annotations for SV/CNVs are similar to those of SNVs with the following differences:

Gene annotation: The summary display shows the gene name of the gene for which the disorder annotation is considered most relevant for the input phenotype. If multiple genes are involved in the SV/CNV, the summary display also indicates the number of genes affected by the variant.

Size: Below the chromosomal location of the SV/CNV, an indication of the size of the variant will be displayed.

Genotype: The genotype for SV/CNVs is defined by the type of the variant (eg. duplication, deletion) and the copy number. The copy number is extracted from the input VCF file if possible, otherwise, it is arbitrarily set by Moon based on the type of the variation and expected reference copy number.

Disorder name with link to OMIM/PubMed. For SV/CNVs overlapping multiple genes, the summary display only shows the disorder with the best match based on concordance between the genotype of the patient and inputted clinical features.