Table 3.

Case-level classification and clinical-level classification

Categories	Case-level classification (Laboratory)	Case-level description	Clinical-level classification (Geneticist)	Clinical-level description
Category 1 (Definitive result)	Definitive	Pathogenic or variant(s) likely pathogenic in a known disease gene associated with the reported phenotype.	Definitive	Pathogenic or variant(s) likely pathogenic in a known disease gene associated with the reported phenotype, after post-exome phenotype review, biochemical, radiological or functional studies is in accordance with the molecular diagnosis.
Category 2 (Possible/probable diagnosis)	Possible	Variant(s) in a known disease gene possibly associated with the reported phenotype. This category includes novel variants in disease genes that overlap the phenotype provided for the proband.	Likely	Novel variant(s) in known disease genes determined to be likely associated with patient phenotype, but evidence is insufficient for a definitive diagnosis after post-exome analysis.
Category 3 (Variant of uncertain significance or novel candidate gene)	Candidate	Variant(s) predicted to be deleterious in a novel candidate gene that have not previously been implicated in human disease or any variant for which the published data is insufficient to support human disease association.	Candidate	Variant(s) in novel candidate genes insufficient to support human disease association despite extensive post-exome analysis.
Category 4 (Negative result)	Negative	No variants in genes associated with the reported phenotype identified	Unlikely	Candidate variants deemed implausible and excluded after post-exome analysis.
			Negative	No variants in genes associated with the reported phenotype identified despite post-exome review.

The ‘case-level’ and ‘clinical-level’ classifications according to Baldridge et al. The ‘case-level’ assertion was a synthesis of all the molecular data in a single subject by the laboratory only. The clinical-level assertion refers to a later stage where the geneticists reassess the classifications using criteria such as: the phenotype-genotype correlation, follow-up biochemical, radiological and functional studies, and additional molecular studies (e.g. X-inactivation). These cannot be determined at the ‘case-level’ from the initial laboratory report. The term ‘unlikely’ (Category 4) was used for molecular diagnosis deemed implausible after review