Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002231254 | SCV000629373 | pathogenic | Rubinstein-Taybi syndrome | 2017-05-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with a CREBBP-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the CREBBP (p.Ser1898Argfs*14). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 545 amino acids of the CREBBP protein. Two different truncations downstream of this variant (p.Ser2015Alafs*25 and  p.Gln2022Argfs*16) have been determined to be pathogenic (PMID: 17052327). This suggests that deletion of this region of the CREBBP protein is causative of disease. |