Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000531426 | SCV000657498 | likely pathogenic | Cornelia de Lange syndrome 1 | 2017-02-24 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with proline at codon 1792 of the NIPBL protein (p.Ala1792Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a NIPBL-related disease. However, family studies have indicated that this variant was not present in the parents of an individual with clinical features of Cornelia de Lange syndrome, which suggests that it was de novo in that affected individual (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change that is absent from the population and has been observed to be de novo in an affected individual. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |