Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Breda Genetics srl | RCV001723252 | SCV001950178 | uncertain significance | Developmental and epileptic encephalopathy, 73 | 2021-09-03 | criteria provided, single submitter | clinical testing | The variant c.950_951del (p.Ser317Cysfs*25) creates a shift in the reading frame which is predicted to result in a premature stop codon 25 amino acids downstream, which is likely to result in a truncated protein or protein loss due to nonsense-mediated messenger decay (NMD). This variant has not been reported in dbSNP, gnomAD, 1000 Genomes Project or ClinVar. To our best knowledge, all mutations reported so far are missense mutations, which act through a gain-of-function mechanism, while in no patient have loss-of-function mutations been described (PMID: 30595371). For these reasons, we interpret the variant at least as uncertain, even if we cannot exclude the possibility that variants loss-of-function in the RNF13 gene, such as that identified in the patient, may cause a clinical picture different from that known to date of developmental epileptic encephalopathy 73 (phenotype expansion). |