Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Broad Center for Mendelian Genomics, |
RCV000993722 | SCV001146911 | likely pathogenic | See cases | 2019-02-07 | criteria provided, single submitter | research | The heterozygous p.Lys593Argfs*17 variant in KMT2E was identified by our research study in a female and an unrelated male with intellectual disabilities and epilepsy. Of note, the female individual received clinical sequencing through Mendelics. Trio exome analysis showed this variant to be de novo in both of the patients. The p.Lys593Argfs*17 variant in KMT2E has not been previously reported in individuals with intellectual disabilities or epilepsy and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 593 and leads to a premature termination codon 17 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. This alteration is then predicted to lead to a truncated or absent protein. It is of note, that loss of function of the KMT2E gene in autosomal dominant disease has not yet been established based on the criteria laid out in Tayoun, 2018 (PMID: 30192042). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. |
| Gene |
RCV001662801 | SCV001873549 | pathogenic | not provided | 2021-09-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); Frameshift 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; This variant is associated with the following publications: (PMID: 31079897) |
| Genetics Laboratory, |
RCV000790637 | SCV002577704 | pathogenic | O'Donnell-Luria-Rodan syndrome | 2022-10-04 | criteria provided, single submitter | clinical testing | PVS1;PS4_moderate;PM6;PM2_supporting |
| Institute for Medical Genetics and Human Genetics, |
RCV000790637 | SCV002578178 | pathogenic | O'Donnell-Luria-Rodan syndrome | 2022-09-27 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001662801 | SCV004010707 | pathogenic | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | KMT2E: PVS1, PM2, PS4:Moderate, PM6:Supporting |
| Mendelics | RCV000754714 | SCV000882562 | likely pathogenic | Epilepsy; intellectual deficiency | 2019-01-29 | no assertion criteria provided | clinical testing | |
| OMIM | RCV000790637 | SCV000929984 | pathogenic | O'Donnell-Luria-Rodan syndrome | 2019-07-25 | no assertion criteria provided | literature only |