Submissions for variant NM_003482.4(KMT2D):c.12268C>T (p.Gln4090Ter)

dbSNP: rs1555188155

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine	RCV000578134	SCV000583532	likely pathogenic	Kabuki syndrome 1		criteria provided, single submitter	research
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000578134	SCV001245026	pathogenic	Kabuki syndrome 1	2018-11-12	criteria provided, single submitter	clinical testing	A heterozygous nonsense variant, NM_003482.3(KMT2D):c.12268C>T, has been identified in exon 39 of 54 of the KMT2D gene. The variant is predicted to result in a premature stop codon at position 4090 of the protein (NP_003473.3(KMT2D):p.(Gln4090*)). This variant is predicted to result in loss of protein function through nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is absent in the gnomAD population database, and has previously been described as likely pathogenic (ClinVar). Many up- and downstream variants resulting in a premature termination codon have been reported in patients with Kabuki syndrome (ClinVar). Analysis of parental samples indicated this variant is de novo. Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.