Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523187 | SCV000619885 | likely pathogenic | not provided | 2018-04-05 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has been identified in the NRXN1 gene. The R1293X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1293X nonsense variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the R1293X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
Invitae | RCV001857997 | SCV002236222 | pathogenic | Pitt-Hopkins-like syndrome 2 | 2022-10-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 451216). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1293*) in the NRXN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NRXN1 are known to be pathogenic (PMID: 19896112, 21964664, 23495017, 23533028, 25149956, 30031152). |