Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000493961 | SCV000581880 | pathogenic | not provided | 2020-03-18 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27311832, 29460469) |
| Labcorp Genetics |
RCV003758800 | SCV004400566 | likely pathogenic | Rubinstein-Taybi syndrome | 2023-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1867 of the CREBBP protein (p.Arg1867Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of CREBBP-related conditions (PMID: 27311832, 29460469). ClinVar contains an entry for this variant (Variation ID: 429336). 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 CREBBP protein function. This variant disrupts the p.Arg1867 amino acid residue in CREBBP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27311832). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| OMIM | RCV000757966 | SCV000886491 | pathogenic | Menke-Hennekam syndrome 1 | 2019-02-22 | no assertion criteria provided | literature only | |
| Al Jawhara Center for Molecular Medicine, |
RCV000757966 | SCV003762115 | uncertain significance | Menke-Hennekam syndrome 1 | 2023-01-20 | no assertion criteria provided | clinical testing |