Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV001420558 | SCV001622864 | uncertain significance | Rubinstein-Taybi syndrome due to CREBBP mutations | 2020-05-12 | criteria provided, single submitter | clinical testing | The c.6839G>A (p.Gly2280Glu) variant identified in the CREBBP gene substitutes a very well conserved Glycine for Glutamic Acid at amino acid 2280/2443 (coding exon 31/31). This variant is absent from gnomAD (v3.0) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Deleterious (Provean; score:-3.56) and Damaging (SIFT; score:0.001) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has notbeen reported in affected individuals in the literature. The p.Gly2280 residue is not within a mapped domain of CREBBP (UniProtKB: Q92793). Given the lack of compelling evidence for its pathogenicity, the c.6839G>A (p.Gly2280Glu) variant identified in the CREBBP gene is reported here as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV002554090 | SCV003469801 | likely benign | Rubinstein-Taybi syndrome | 2024-10-22 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004743472 | SCV005363034 | uncertain significance | CREBBP-related disorder | 2024-03-12 | no assertion criteria provided | clinical testing | The CREBBP c.6839G>A variant is predicted to result in the amino acid substitution p.Gly2280Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |