Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000627349 | SCV000748341 | pathogenic | not provided | 2018-04-16 | criteria provided, single submitter | clinical testing | The R1837X variant in the NIPBL gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R1837X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R1837X as a pathogenic variant. |
| Invitae | RCV001380292 | SCV001578295 | pathogenic | Cornelia de Lange syndrome 1 | 2020-03-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in NIPBL are known to be pathogenic (PMID: 15318302, 19763162, 23505322, 29995837). This variant has been observed in individual(s) with Cornelia de Lange syndrome (PMID: 31337854). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 523876). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg1837*) in the NIPBL gene. It is expected to result in an absent or disrupted protein product. |
| Genome- |
RCV001380292 | SCV002054158 | pathogenic | Cornelia de Lange syndrome 1 | 2021-07-15 | criteria provided, single submitter | clinical testing |