Features of VIP-HL web interface
Users can search the interface (http://hearing.genetics.bgi.com/) by gene name, chromosomal location, dbSNP identifier, and HGVS nomenclature (den Dunnen et al., 2016). If a gene is queried, the results will present the gene name, cytobands, protein name, external databases and the variant list. The variant list consists all the pre-annotated variants displayed with their pathogenicity and corresponding ACMG/AMP rules. For variants not pre-annotated, VIP-HL can execute the algorithm and provide the interpreting results promptly. Once variants that are not pre-annotated are queried, they will be automatically added to the variant list. If a specific variant is queried, VIP-HL displays the variant location (variant identifier), gene name, inheritance, cHGVS, pHGVS, ACMG/AMP criteria, and classifications (Figure 3).
The browser displays six sections, including necessary information, population, computation, case/segregation, function, and community sections (Figure 3). The automatically annotated ACMG/AMP rules are presented in the population and computation sections, providing detailed explanations of the ratings based on the guidelines of genetic hearing loss (Oza et al., 2018). Rules that require manual curation are presented in the case/segregation and function sections. The community section records the submissions by users who would like to share their classifications with others.
Users are free to adjust the evidence strength from “Supporting” to “VeryStrong” in 24 ACMG/AMP rules. The classifications will update instantly with any rule(s) modifications. For rules grouped in the case/segregation and function sections, evidence to support the strength level can be manually added, enabling users to record and manage their curations.