ClinVar Miner

Submissions for variant NM_003482.4(KMT2D):c.2994del (p.Pro998_Met999insTer)

gnomAD frequency: 0.00001  dbSNP: rs1057519595
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center of Genomic medicine, Geneva, University Hospital of Geneva RCV000417094 SCV000494651 pathogenic Kabuki syndrome 1 2015-11-19 criteria provided, single submitter clinical testing Patient with symptoms consistent with the Kabuki syndrome. Loss of function mutations in KMT2D (MLL2) are known to cause Kabuki syndrome and here we report a mutation causing a truncated and non-functional MLL2 protein.
Genomic Medicine Lab, University of California San Francisco RCV000417094 SCV001167611 pathogenic Kabuki syndrome 1 2018-08-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001056522 SCV001220967 pathogenic Kabuki syndrome 2019-06-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Met999*) in the KMT2D gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Kabuki syndrome (PMID: 27353043). ClinVar contains an entry for this variant (Variation ID: 375634). Loss-of-function variants in KMT2D are known to be pathogenic (PMID: 22126750). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV004730944 SCV005339057 pathogenic KMT2D-related disorder 2024-09-23 no assertion criteria provided clinical testing The KMT2D c.2994delT variant is predicted to result in premature protein termination (p.Met999*). This variant has been reported to be causative for Kabuki syndrome (Fokstuen et al. 2016. PubMed ID: 27353043; Table S14, Slavotinek et al. 2023. PubMed ID: 37236975). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in KMT2D are expected to be pathogenic. This variant is interpreted as pathogenic.

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