Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics, |
RCV001733801 | SCV001984748 | likely pathogenic | O'Donnell-Luria-Rodan syndrome | 2021-10-27 | criteria provided, single submitter | clinical testing | The variant c.3489dup (p.(Lys1164*)) in exon 22 of the KMT2E gene is not found in the gnomAD database and interrupts the reading frame prematurely at position 1164. Truncating mutations within this gene are a known mechanism of disease: Pathogenic mutations in the KMT2E gene are causative for the autosomal dominant inherited O'Donnell-Luria-Rodan syndrome - a neurodevelopmental disorder, which can be associated in affected individuals with a language development disorder, an intellectual impairment of highly variable extent, infantile hypotonia, gastrointestinal anomalies and subtle dysmorphic features (here in particular with a prominent, high forehead). While epilepsies have been described mainly in female carriers of pathogenic KMT2E mutations, autistic traits have been observed particularly often in male patients. Missense mutations in KMT2E have been associated with microcephaly and a greater developmental delay in affected individuals, whereas truncating KMT2E sequence alterations caused a comparatively milder phenotype and macrocephaly. Most pathogenic KMT2E variants described to date were de novo in patients (O'Donnell-Luria et al. (2019) Am J Hum Genet 104:1210, PMID: 31079897). A de novo testing in our patient was not possible. ACMG criteria used for classification: PVS1, PM2, PP3. |
| Gene |
RCV003238869 | SCV003936409 | pathogenic | not provided | 2023-06-30 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; 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 |