Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000551293 | SCV000657505 | likely pathogenic | Cornelia de Lange syndrome 1 | 2017-10-27 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NIPBL-related disease. However, it has been observed to be de novo in an individual affected with NIPBL-related disease (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 2611 of the NIPBL protein (p.Lys2611Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. |