Submissions for variant NM_182931.3(KMT2E):c.4397_4398insCACAGCATGGTTATCTTTC (p.Pro1467fs)

dbSNP: rs1584817521

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000993734	SCV001146923	likely pathogenic	See cases	2019-02-07	criteria provided, single submitter	research	The heterozygous p.Pro1467Thrfs*75 variant in KMT2E was identified by our study in one individual with developmental delays and intellectual disability. Trio exome analysis showed this variant to be de novo. The p.Pro1467Thrfs*75 variant in KMT2E has not been previously reported in individuals with developmental delays or intellectual disability and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1467 and leads to a premature termination codon 75 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. This alteration is then predicted to lead to a truncated or absent protein. It is of note, that loss of function of the KMT2E gene in autosomal dominant disease has not yet been established based on the criteria laid out in Tayoun, 2018 (PMID: 30192042). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic.