ClinVar Miner

Submissions for variant NM_003482.4(KMT2D):c.4135_4136del (p.Met1379fs)

dbSNP: rs398123744
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000146210 SCV000193446 pathogenic Kabuki syndrome 1 2013-08-29 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000790669 SCV000226100 pathogenic not provided 2015-03-30 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000146210 SCV000781562 likely pathogenic Kabuki syndrome 1 2016-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000799267 SCV000938921 pathogenic Kabuki syndrome 2024-04-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Met1379Valfs*52) in the KMT2D gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KMT2D are known to be pathogenic (PMID: 22126750). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Kabuki syndrome (PMID: 24633898, 26512256, 27302555). ClinVar contains an entry for this variant (Variation ID: 94216). For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics and Genomics, Karolinska University Hospital RCV000790669 SCV001450315 pathogenic not provided 2016-03-30 criteria provided, single submitter clinical testing
GeneDx RCV000790669 SCV004028256 pathogenic not provided 2023-02-16 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32459397, 24633898, 27302555, 32005694, 24739679, 32170002, 26512256, 33726816)
Neuberg Centre For Genomic Medicine, NCGM RCV000146210 SCV005400734 pathogenic Kabuki syndrome 1 2023-06-22 criteria provided, single submitter clinical testing The observed frameshift variant c.4135_4136del(p.Met1379ValfsTer52) in the KMT2D gene has been reported previously in individuals with Kabuki syndrome (Cheon CK, Ko JM., 2015; Bögershausen N, et al., 2016). This variant is absent in the gnomAD Exomes. This variant causes a frameshift starting with codon Methionine 1379, changes this amino acid to Valine residue, and creates a premature Stop codon at position 52 of the new reading frame, denoted p.Met1379ValfsTer52. It is submitted to ClinVar as Pathogenic/Likely pathogenic. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Autoinflammatory diseases unit, CHU de Montpellier RCV000146210 SCV001438172 pathogenic Kabuki syndrome 1 2013-10-01 no assertion criteria provided clinical testing

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