ClinVar Miner

Submissions for variant NM_001079846.1(CREBBP):c.4280G>A (p.Gly1427Glu) (rs1555473491)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633000 SCV000754210 pathogenic Rubinstein-Taybi syndrome 1 2017-11-15 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 1465 of the CREBBP protein (p.Gly1465Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant also falls at the last nucleotide of exon 26 of the CREBBP coding sequence, which is part of the consensus splice site for this exon. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CREBBP-related disease. However, it has been observed to be de novo in an individual with clinical features of Rubinstein-Taybi syndrome (Invitae). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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