CanVar-UK: A collaborative platform for germline interpretation in cancer susceptibility genes.

Aggregation of in silico scores, population frequencies, functional data and case counts, coupled to a traceable inter-laboratory classification forum

CanVar-UK is a freely accessible web platform designed to support interpretation of germline variants in cancer susceptibility genes. It holds variant-level data for over 1.1 million single-nucleotide variants, covering all possible coding SNVs in 116 established cancer susceptibility genes. Each variant is annotated with in silico scores from 11 clinically relevant tools, gnomAD v4.1 population allele frequencies, case counts from multiple cohorts including NHS clinical laboratory testing, readouts from 47 selected functional and splicing datasets across 19 genes, genetic epidemiology studies, and a live link to consensus classifications in ClinVar. A diagnostic discussion forum, restricted to registered diagnostic scientists, allows a variant-tagged message to be dispatched in real time to a community of more than 1,500 users, with all exchanges and classifications captured in the platform. Already widely used by NHS diagnostic scientists, it has more than 800 registered UK users and more than 600 outside the UK.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

What sets CanVar-UK apart from existing aggregators is the traceable forum: classification discordance between laboratories is the real problem in cross-border cascade testing, and recording who classified what and why is worth more than one more in silico score. The trade-off is that this is a resource, not a study: no before/after concordance measurement, no data on the proportion of variants of uncertain significance actually resolved. Its scope — coding substitutions in 116 genes — by construction leaves out deep intronic and structural variants, a growing share of unresolved cases.

Analysis by Dr Thibaut Benquey