ClinVar Miner

Submissions for variant NM_001079846.1(CREBBP):c.3718G>A (p.Glu1240Lys) (rs267606752)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255660 SCV000321525 pathogenic not provided 2018-01-10 criteria provided, single submitter clinical testing The E1278K missense variant in the CREBBP gene has been reported previously in association with Rubinstein-Taybi syndrome (Kalkhoven et al., 2003; Schorry et al., 2008). The E1278K variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. E1278K is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a conserved position within the plant homeodomain-type zinc finger region of the HAT domain (Kalkhoven et al., 2002). While functional studies involving the E1278 residue are conflicting (Kalkhoven et al., 2003; Rack et al., 2014), in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in the same residue (E1278A/G) have also been reported in the Human Gene Mutation Database in association with Rubinstein-Taybi syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein.
Genetic Services Laboratory, University of Chicago RCV000010040 SCV000192864 pathogenic Rubinstein-Taybi syndrome 1 2013-02-08 criteria provided, single submitter clinical testing
OMIM RCV000010040 SCV000030261 pathogenic Rubinstein-Taybi syndrome 1 2003-02-15 no assertion criteria provided literature only

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