Submissions for variant NM_182931.3(KMT2E):c.280del (p.Thr94fs)

dbSNP: rs1584746915

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000993715	SCV001146904	uncertain significance	See cases	2019-02-07	criteria provided, single submitter	research	The heterozygous p.Thr94fs*25 variant in KMT2E was identified by our study in one individual with intellectual disabilities. The variant is assumed de novo in the individual, but maternity and paternity have not been confirmed. The p.Thr94fs*25 variant in KMT2E has not been previously reported in individuals with intellectual disabilities 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 94 and leads to a premature termination codon 25 amino acids downstream. 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).This alteration is then predicted to lead to a truncated or absent protein. In summary, the clinical significance of the p.Thr94fs*25 variant is uncertain.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001268240	SCV001447027	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing