TABLE 3.

Five-dimensional evaluation of phenotypes of DEPDC5 variants.

	MCD	FEFS + /FS
1. Repetition: variants recurrently identified in unrelated cases of homogenous phenotype, or significantly high frequency or hotspot in patients	Yes. Identified in 39 unrelated cases from different cohorts	Yes. Nine unrelated cases from different reports.
2. Genotype–phenotype correlation: for heterogeneous phenotypes, a phenotype was within the spectrum that is correlated with genotype	Yes. Homozygous mutation and second-hit brain mosaic mutations, possible high frequency of null mutations	Yes. Mainly missense mutations
3. Inheritance pattern: cosegregation in families with AD/AR inheritance, or de novo origination	Yes. Mainly in families with AD inheritance, de novo in five cases	Yes. Mainly in families with AD inheritance, de novo in three cases
4. Genetic quantitative correlation: correlation between genetic impairment and phenotype severity	Yes. Tendency of high frequency of null mutations, or bi-allelic mutations (including brain mosaicism) in severe phenotype	Yes. The mild phenotype with mainly missense mutations that were potentially less functionally impaired
5. Molecular sub-regional implications: sub-regional or sub-molecular effects of genetic variants, or distinct functional alteration/mechanism	Possible. Heterozygous missense variants clustered in SABA domain and were close to the binding sites to NPRL2/NPRL3 complex	Possible. Heterozygous missense variants located away from NPRL2/NPRL3 complex or RAGA/RAGC complex

Abbreviations: MCD, malformation of cortical development; FEFS + /FS, focal epilepsy with febrile seizures plus/febrile seizures; AD, autosomal dominant; AR, autosomal recessive; SABA, structural axis for binding arrangement.