Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000519716 | SCV000617845 | pathogenic | not provided | 2019-08-02 | criteria provided, single submitter | clinical testing | Reported previously, in the heterozygous state, in one individual with Kabuki syndrome (Banka et al., 2012); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22126750) |
| Center for Human Genetics, |
RCV000659761 | SCV000781611 | pathogenic | Kabuki syndrome 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
| Lifecell International Pvt. |
RCV000659761 | SCV003852650 | likely pathogenic | Kabuki syndrome 1 | criteria provided, single submitter | clinical testing | A Heterozygous Nonsense variant c.8059C>T in Exon 33 of the KMT2D gene that results in the amino acid substitution p.Arg2687* was identified. The observed variant is novel in gnomAD exomes and genomes. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic [Variant ID :449562]. For these reasons this variant has been classified as Likely Pathogenic. | |
| Institute of Medical Genetics and Genomics, |
RCV000659761 | SCV003935004 | pathogenic | Kabuki syndrome 1 | criteria provided, single submitter | clinical testing | The heterozygous de-novo variant c.8059C>T (p.Arg2687*) is identified in a proband with atrial septal defect, cleft palate, coronal craniosynostosis, bilateral coloboma, micrognathia, pyriform aperture stenosis. This stop gain variant is predicted to cause NMD in the gene KMT2D where loss of function is a known mechanism (PVS1_very strong). This variant has not been identified in gnomAD population database (PM2_moderate). However, this has been reported in ClinVar id 449562 thrice (PP5_supporting). | |
| Baylor Genetics | RCV000659761 | SCV004040943 | pathogenic | Kabuki syndrome 1 | 2023-07-11 | criteria provided, single submitter | clinical testing |