Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000798739 | SCV000938369 | pathogenic | Cornelia de Lange syndrome 1 | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2233 of the NIPBL protein (p.Val2233Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Cornelia de Lange Syndrome (PMID: 20824775, 32074972; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 644755). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NIPBL protein function. For these reasons, this variant has been classified as Pathogenic. |
| Prevention |
RCV003411756 | SCV004112963 | likely pathogenic | NIPBL-related condition | 2022-11-08 | criteria provided, single submitter | clinical testing | The NIPBL c.6697G>A variant is predicted to result in the amino acid substitution p.Val2233Met. This variant has been previously reported in two individuals with Cornelia de Lange syndrome, reported as a de novo finding in (Thanh et al. 2020. PubMed ID: 32074972) and of unknown origin in (Oliveira et al. 2010. PubMed ID: 20824775). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic. |