ClinVar Miner

Submissions for variant NM_001197104.2(KMT2A):c.3461G>A (p.Arg1154Gln)

dbSNP: rs1131691799
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493579 SCV000582874 pathogenic not provided 2022-01-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30315573)
Ambry Genetics RCV000623546 SCV000741430 pathogenic Inborn genetic diseases 2016-05-04 criteria provided, single submitter clinical testing
Mendelics RCV002248724 SCV002516625 pathogenic Wiedemann-Steiner syndrome 2022-05-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000493579 SCV004551681 pathogenic not provided 2023-09-30 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of Cornelia de Lange syndrome (PMID: 30315573). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg1154 amino acid residue in KMT2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29203834, 29574747, 33043602). 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 KMT2A protein function. ClinVar contains an entry for this variant (Variation ID: 430144). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1154 of the KMT2A protein (p.Arg1154Gln).
Genetic Services Laboratory, University of Chicago RCV000504302 SCV000595438 uncertain significance not specified 2016-07-11 flagged submission clinical testing

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