ClinVar Miner

Submissions for variant NM_003482.4(KMT2D):c.15640C>T (p.Arg5214Cys)

dbSNP: rs398123728
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659827 SCV000781690 pathogenic Kabuki syndrome 1 2016-11-01 criteria provided, single submitter clinical testing
Wangler Lab, Baylor College of Medicine RCV000659827 SCV002762717 pathogenic Kabuki syndrome 1 criteria provided, single submitter clinical testing This missense KMT2D variant at c.15640C>T (p.R5214C) was seen on exome through the Texome project (R01HG011795). This variant was de novo in the patient (PS2) and has been previously reported in individuals with Kabuki syndrome 1 (PMID: 21671394, 23320472, 27302555, 30107592).This variant has not been observed in gnomAD (PM2). It is predicted to be deleterious by multiple computational models (CADD: 32.000) (PP3), and the evolutionary conservation of this residue is high. Therefore, we classify this variant as pathogenic.
Baylor Genetics RCV000659827 SCV003836049 pathogenic Kabuki syndrome 1 2022-12-03 criteria provided, single submitter clinical testing
Invitae RCV003588663 SCV004295029 pathogenic Kabuki syndrome 2023-06-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg5214 amino acid residue in KMT2D. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20711175, 30107592, 30950893). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KMT2D protein function. ClinVar contains an entry for this variant (Variation ID: 547505). This missense change has been observed in individual(s) with Kabuki syndrome (PMID: 21671394). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 5214 of the KMT2D protein (p.Arg5214Cys).
Autoinflammatory diseases unit, CHU de Montpellier RCV000659827 SCV001438153 pathogenic Kabuki syndrome 1 2014-11-25 no assertion criteria provided clinical testing

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