QV ES evidence interpretation table (rare single case interpretation)
Each rule maps raw flags (TRUE, FALSE, NA) to binary evidence indicators based on whether the observed data contradict the underlying hypothesis.
Rule names describe what a TRUE flag detects.
A value of 1 indicates that no contradiction is observed.
Missing data (NA) never counts as evidence present.
| rule name | flag | meaning | X_ij |
|---|---|---|---|
| gnomad flag present | TRUE | at least one gnomAD quality or annotation flag is present | 0 |
| gnomad flag present | FALSE | no gnomAD flags observed | 1 |
| gnomad flag present | NA | gnomAD flag status unavailable | 0 |
| acmg benign evidence present | TRUE | ACMG benign evidence code detected | 0 |
| acmg benign evidence present | FALSE | no ACMG benign evidence detected | 1 |
| acmg benign evidence present | NA | ACMG evidence unavailable | 0 |
| ppie requirement unmet | TRUE | patient or public involvement requirement not fulfilled | 0 |
| ppie requirement unmet | FALSE | PPIE requirement fulfilled or not applicable | 1 |
| ppie requirement unmet | NA | PPIE status not recorded | 0 |
| proband genotype invalid | TRUE | proband genotype missing or non interpretable | 0 |
| proband genotype invalid | FALSE | proband genotype valid | 1 |
| proband genotype invalid | NA | proband genotype unavailable | 0 |
| parent gt unavailable mother | TRUE | maternal genotype unavailable | 0 |
| parent gt unavailable mother | FALSE | maternal genotype available | 1 |
| parent gt unavailable mother | NA | availability unknown | 0 |
| parent gt unavailable father | TRUE | paternal genotype unavailable | 0 |
| parent gt unavailable father | FALSE | paternal genotype available | 1 |
| parent gt unavailable father | NA | availability unknown | 0 |
| parent gt unavailable any | TRUE | at least one parental genotype unavailable | 0 |
| parent gt unavailable any | FALSE | both parental genotypes available | 1 |
| parent gt unavailable any | NA | availability unknown | 0 |
| parent gt homozygous | TRUE | a parent is homozygous for the variant | 0 |
| parent gt homozygous | FALSE | no parent homozygous for the variant | 1 |
| parent gt homozygous | NA | parental genotype unavailable | 0 |
| parent gt mechanistically inconsistent ar | TRUE | parental genotypes contradict autosomal recessive inheritance | 0 |
| parent gt mechanistically inconsistent ar | FALSE | no contradiction with autosomal recessive inheritance observed | 1 |
| parent gt mechanistically inconsistent ar | NA | parental genotype unavailable | 0 |
| unaffected relative homozygous alt | TRUE | unaffected parent or close relative carries the same homozygous ALT | 0 |
| unaffected relative homozygous alt | FALSE | no unaffected relative with the same genotype observed | 1 |
| unaffected relative homozygous alt | NA | phenotype or genotype information unavailable | 0 |
| compound het phase inconsistent | TRUE | phase or configuration contradicts compound heterozygosity | 0 |
| compound het phase inconsistent | FALSE | no phase contradiction observed | 1 |
| compound het phase inconsistent | NA | phase information unavailable | 0 |
| denovo mechanism excluded | TRUE | parental genotypes exclude a de novo mechanism | 0 |
| denovo mechanism excluded | FALSE | de novo mechanism not excluded | 1 |
| denovo mechanism excluded | NA | parental genotypes unavailable | 0 |
| population frequency common | TRUE | population frequency incompatible with rare disease | 0 |
| population frequency common | FALSE | population frequency compatible with rare disease | 1 |
| population frequency common | NA | population frequency unavailable | 0 |
| population frequency unavailable | TRUE | no population frequency information available | 0 |
| population frequency unavailable | FALSE | population frequency available | 1 |
| population frequency unavailable | NA | population frequency unknown | 0 |
| transcript not expressed in controls | TRUE | transcript not detected in any control sample | 0 |
| transcript not expressed in controls | FALSE | transcript detected in controls | 1 |
| transcript not expressed in controls | NA | control expression unavailable | 0 |
| transcript not quantifiable in patient | TRUE | patient transcript not quantifiable | 0 |
| transcript not quantifiable in patient | FALSE | patient transcript quantifiable | 1 |
| transcript not quantifiable in patient | NA | patient expression unavailable | 0 |
| transcript non canonical | TRUE | variant does not affect MANE or curated clinical transcript | 0 |
| transcript non canonical | FALSE | variant affects MANE or curated clinical transcript | 1 |
| transcript non canonical | NA | transcript relevance unknown | 0 |
| genedisease validity weak | TRUE | ClinGen gene disease validity not strong or definitive | 0 |
| genedisease validity weak | FALSE | ClinGen gene disease validity strong or definitive | 1 |
| genedisease validity weak | NA | ClinGen validity unavailable | 0 |
| omim inconsistency | TRUE | OMIM disease entry missing or mode of inheritance mismatch | 0 |
| omim inconsistency | FALSE | OMIM disease entry present with matching inheritance | 1 |
| omim inconsistency | NA | OMIM information unavailable | 0 |
| lof mechanism inconsistent | TRUE | loss of function mechanism inconsistent with known gene biology | 0 |
| lof mechanism inconsistent | FALSE | loss of function consistent with known gene mechanism | 1 |
| lof mechanism inconsistent | NA | loss of function context unavailable | 0 |
| clinvar benign conflict | TRUE | ClinVar contains benign or conflicting interpretations | 0 |
| clinvar benign conflict | FALSE | no benign conflict in ClinVar | 1 |
| clinvar benign conflict | NA | ClinVar information unavailable | 0 |
| phenotype mismatch | TRUE | phenotype similarity below threshold | 0 |
| phenotype mismatch | FALSE | phenotype similarity sufficient | 1 |
| phenotype mismatch | NA | phenotype information unavailable | 0 |
| disease spectrum mismatch | TRUE | clinical presentation inconsistent with known disease spectrum | 0 |
| disease spectrum mismatch | FALSE | clinical presentation consistent | 1 |
| disease spectrum mismatch | NA | disease spectrum information unavailable | 0 |
| present in controls | TRUE | variant observed in unrelated controls | 0 |
| present in controls | FALSE | variant absent from controls | 1 |
| present in controls | NA | control data unavailable | 0 |
| hgmd support absent | TRUE | no HGMD disease association | 0 |
| hgmd support absent | FALSE | HGMD disease association reported | 1 |
| hgmd support absent | NA | HGMD data unavailable | 0 |
| literature mechanism discordant | TRUE | published mechanism conflicts with proposed effect | 0 |
| literature mechanism discordant | FALSE | published evidence concordant | 1 |
| literature mechanism discordant | NA | literature evidence unavailable | 0 |
