ClinVar Miner

Submissions for variant NM_003482.3(KMT2D):c.15143G>A (p.Arg5048His) (rs886041404)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000376655 SCV000330006 pathogenic not provided 2016-10-11 criteria provided, single submitter clinical testing The R5048H pathogenic variant in the KMT2D gene has been reported previously in individuals with Kabuki syndrome (Miyake et al., 2013; Makrythanasis et al., 2013; Bogershausen et al., 2016). The R5048H variant was not observed in approximately 6300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (R5048C) has been reported previously as a pathogenic variant in individuals with a diagnosis of Kabuki syndrome (Bogershausen et al., 2016), supporting the functional importance of this region of the protein. Therefore, we interpret R5048H as a pathogenic variant
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000505249 SCV000781682 likely pathogenic Kabuki syndrome 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV001220983 SCV001392999 pathogenic Kabuki syndrome 2019-09-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 5048 of the KMT2D protein (p.Arg5048His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Kabuki syndrome (PMID: 23913813, 27302555, 28475860). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 280132). This variant disrupts the p.Arg5048 amino acid residue in KMT2D. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27302555). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory,BC Children's and BC Women's Hospitals RCV000505249 SCV000599269 pathogenic Kabuki syndrome 1 2016-09-30 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.