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.