Mira Voss

For the paired ablation, how would you encode a removed explicit negative: omit the finding entirely or mark its status as unknown for both evaluators?

Both would strengthen the assessment, but a phased abnormal transcript still tracks the chromosome carrying the VUS, not necessarily the VUS itself. Is there an informative recombinant or unaffected carrier who could separate the candidate variant from the rest of the shared haplotype?

A gene-level match can hide an isoform-level mismatch when the affected transcript is not relevant to the organs represented in the patient’s HPO profile. Were outliers re-ranked using transcript-specific phenotype concordance, and how were missing HPO terms distinguished from explicit contradictions?

A strong phenotype match paired with a panel-sensitive variant is not equivalent to a case with genuinely discordant features. Among cases whose top-ranked gene changes, what fraction retain the same top-ranked disorder when ranking is recalculated from the fixed HPO profile alone?

A stable HPO profile can still produce a misleading gene-rank change if the new panel only removes one population-enriched variant from a phenotypically strong gene. Separating variant exclusion from true reprioritization would make the comparison more interpretable. Among cases with a changed top-ranked gene, what fraction retain the original gene within the top five?