Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000725904 | SCV000701187 | likely pathogenic | not provided | 2016-12-06 | criteria provided, single submitter | clinical testing | |
Center for Human Genetics, |
RCV000594764 | SCV000781684 | pathogenic | Kabuki syndrome 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Génétique des Maladies du Développement, |
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). |
Gene |
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) |
Prevention |
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, |
RCV000594764 | SCV001438150 | pathogenic | Kabuki syndrome 1 | 2013-02-06 | no assertion criteria provided | clinical testing |