ClinVar Miner

Submissions for variant NM_001429.4(EP300):c.3014_3015del (p.Asp1004_Cys1005insTer)

dbSNP: rs2059050320
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001195547 SCV001365932 pathogenic Rubinstein-Taybi syndrome 2019-04-04 criteria provided, single submitter clinical testing The p.Cys1005X variant in EP300 has not been previously reported in individuals with Rubenstein-Taybi syndrome 2 and is absent from large population studies. However, this variant was confirmed to be de novo in an individual with moderate intellectual disability, autism, corpus callosum hypoplasia, ventriculomegaly, low columella, and dental crowding by the Broad Institute Rare Genomes Project. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1005 and leads to a premature termination codon at this position. This alteration is then predicted to lead to absent protein. Heterozygous loss of function of the EP300 gene is an established disease mechanism in individuals with Rubenstein-Taybi syndrome 2. In summary, this variant meets criteria to be classified as pathogenic for Rubenstein-Taybi syndrome 2 in an autosomal dominant manner based upon de novo occurrence, its absence from the general population, and its predicted impact on the protein. ACMG/AMP Criteria applied: PVS1, PS2, PM2.

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