Interstitial deletions, protein truncating variants (frameshift, splice-site and stop gain variants) and non-synonymous (missense) variants in KMT2B have been identified.
The majority of the variants in KMT2B occur de novo, but rarely autosomal dominant inheritance with reduced/variable penetrance is reported.
No recurring variants or mutational hotspots have been reported to date. Variants are frequently located in key protein domains, including the catalytic SET domain.
Early phenotype-genotype correlation studies indicate that, patients with chromosomal microdeletions and protein truncating variants present at a statistically significant younger age, when compared to those with intragenic missense variants and tend to manifest more systemic and neurological features, including neurodevelopment delay.