Summary Table Rules¶
Tier 1 qualifying variants can be further triaged based on special bioinformatic signatures of interest. These signatures are now fully supported through ATAV. For a description on the requirements to qualify for each of the signatures please refer to attached slideshow.
HZ[E] : 'Hot-Zone' de novo mutations found to affect an Essential gene. Essential defined as a reported lethality gene based on the MGI. Restricted to de novo mutations.
HZ[OMIM] : 'Hot-Zone' de novo mutation found to affect an OMIM disease-associated gene. Restricted to de novo mutations.
OEratio(CDD) <15%tile : A de novo mutation identified in a CDD with an OEratio among the lowest 15%tile. Restricted to de novo mutations.
ClinGen/Var [LoF] : A protein-truncating predicted variant found in a ClinGen defined dosage sensitive gene, or a gene where at least one ClinVar "Pathogenic" loss-of-function allele has been reported. Screen is applied across all four models DNM, HEM, HOM, CHET.
LoF deplet / pLI / pREC : A protein-truncating predicted de novo allele found in a gene reported to be loss-of-function depleted (FDR<0.01, Petrovski et al.), or defined as LoF intolerant based on the ExAC paper (p>0.9). Restricted to de novo mutations. For recessive genotypes (HEM, HOM, CHET), pLI/pREC>0.9
KnownVar (PMID) : Highlights if the variant found in the patient has been previously reported as potentially disease-causal in literature - includes the PUBMED ID of the source paper across. Screen is applied across all four models DNM, HEM, HOM, CHET.
GC Clinical Fit (H/M/L) : GC evaluation requested to assess the relevance to patient's phenotype for all qualifying variants that affect an OMIM disease-associated gene from DNM, HEM, HOM, CHET, MOS, and the Tier 2 genotypes.