ClinVar Miner

Submissions for variant NM_003482.4(KMT2D):c.15461G>A (p.Arg5154Gln)

dbSNP: rs886043497
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725904 SCV000701187 likely pathogenic not provided 2016-12-06 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000594764 SCV000781684 pathogenic Kabuki syndrome 1 2016-11-01 criteria provided, single submitter clinical testing
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV000594764 SCV000890094 pathogenic Kabuki syndrome 1 2018-04-10 criteria provided, single submitter clinical testing
Invitae RCV000808309 SCV000948413 pathogenic Kabuki syndrome 2022-10-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KMT2D protein function. ClinVar contains an entry for this variant (Variation ID: 286834). This missense change has been observed in individual(s) with Kabuki syndrome (PMID: 21607748, 23913813, 25755104, 27302555, 28884922). 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 glutamine, which is neutral and polar, at codon 5154 of the KMT2D protein (p.Arg5154Gln).
GeneDx RCV000725904 SCV001803637 pathogenic not provided 2021-12-14 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 21607748, 27302555, 28991257, 32368696, 30459467)
PreventionGenetics, part of Exact Sciences RCV004535373 SCV004711348 pathogenic KMT2D-related disorder 2024-01-15 criteria provided, single submitter clinical testing The KMT2D c.15461G>A variant is predicted to result in the amino acid substitution p.Arg5154Gln. This variant has been reported in individuals with Kabuki syndrome as a de novo variant and in other cases, family studies were not completed to determine inheritance of the variant (Li et al. 2011. PubMed ID: 21607748; Miyake et al. 2013. PubMed ID: 23913813; Bögershausen et al. 2016. PubMed ID: 27302555; Digilio et al. 2017. PubMed ID: 28884922). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic.
Autoinflammatory diseases unit, CHU de Montpellier RCV000594764 SCV001438150 pathogenic Kabuki syndrome 1 2013-02-06 no assertion criteria provided clinical testing

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