Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001755207 | SCV001996073 | uncertain significance | not provided | 2020-01-06 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Initiation codon variant in a gene for which loss-of-function is not a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge |
Undiagnosed Diseases Network, |
RCV001788835 | SCV002030292 | uncertain significance | Glutamine related condition | 2021-09-07 | criteria provided, single submitter | clinical testing | |
Women's and Children's Health, |
RCV003883701 | SCV004177219 | likely pathogenic | Glutamine synthetase stabilization disorder | 2023-12-01 | no assertion criteria provided | clinical testing | |
OMIM | RCV004526144 | SCV005038961 | pathogenic | Developmental and epileptic encephalopathy 116 | 2024-04-30 | no assertion criteria provided | literature only | |
Prevention |
RCV004731172 | SCV005339609 | pathogenic | GLUL-related disorder | 2024-08-16 | no assertion criteria provided | clinical testing | The GLUL c.3G>A variant is predicted to disrupt the translation initiation site (p.Met1?). This variant was reported to have occurred de novo in an individual with developmental and epileptic encephalopathy, hypotonia, global developmental delay, and brain abnormalities including hypomyelination (Jones et al. 2024. PubMed ID: 38579670). Other variants that impact the start codon have been reported to have occurred de novo in multiple individuals with similar phenotypes (Supplementary Table 1, Kaplanis. 2020. PubMed ID: 33057194; Table S5, Esterhuizen et al. 2023. PubMed ID: 36480001; Jones et al. 2024. PubMed ID: 38579670). Based on functional studies, variants that impact the start codon result in utilization of a downstream methionine (p.Met18) as the initiation codon, and result in a glutamate synthetase enzyme that is insensitive to glutamine-mediated degradation (Jones et al. 2024. PubMed ID: 38579670). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic. |