ClinVar Miner

Submissions for variant NM_004380.3(CREBBP):c.3893A>G (p.Tyr1298Cys)

gnomAD frequency: 0.00001  dbSNP: rs773159964
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001420511 SCV001622812 uncertain significance Rubinstein-Taybi syndrome due to CREBBP mutations 2020-06-19 criteria provided, single submitter clinical testing The inherited c.3893A>G (p.Tyr1298Cys) variant identified in the CREBBP gene substitutes a well conserved Tyrosine for Cystine at amino acid 1298/2443 (coding exon 22/31). This variant is found with low frequency in gnomAD (1 heterozygote, 0 homozygotes; allele frequency: 6.98e-6) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms do not agree on the effect of this variant, as it is predicted Damaging (Provean; score: -4.1), Tolerated (SIFT; score: 0.121) and Pathogenic (REVEL; score: 0.862) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Tyr1298 residue is not within a mapped domain of CREBBP (UniProtKB:Q92793). Given the lack of compelling evidence for its pathogenicity, the inherited c.3893A>G (p.Tyr1298Cys) variant identified in the CREBBP gene is reported here as a Variant of Uncertain Significance.

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