ClinVar Miner

Submissions for variant NM_182931.3(KMT2E):c.544dup (p.Glu182fs)

dbSNP: rs2536417191
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004018304 SCV004847468 likely pathogenic Neurodevelopmental disorder 2024-03-31 criteria provided, single submitter clinical testing The p.Glu182GlyfsX7 variant in KMT2E has not been previously reported in individuals with neurodevelopmental disorders nor in large population studies (gnomAD v4.0.0). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 182 and leads to a premature termination codon 7 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function variants in the KMT2E gene have been reported in many individuals with autosomal dominant complex neurodevelopmental disorder (O'Donnell-Luria 2019 PMID: 31079897). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant KMTE2-related complex neurodevelopmental disorder. ACMG/AMP Criteria applied: PVS1, PM2_Supporting.

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