ClinVar Miner

Submissions for variant NM_004380.3(CREBBP):c.1447C>T (p.Arg483Ter)

dbSNP: rs1555484797
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002231028 SCV000629362 pathogenic Rubinstein-Taybi syndrome 2023-06-23 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 458197). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with Rubinstein-Taybi syndrome (PMID: 31566936). This sequence change creates a premature translational stop signal (p.Arg483*) in the CREBBP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CREBBP are known to be pathogenic (PMID: 17052327, 18792986). This variant is not present in population databases (gnomAD no frequency).
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268046 SCV001446650 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Lifecell International Pvt. Ltd RCV003157633 SCV003845984 pathogenic Rubinstein-Taybi syndrome due to CREBBP mutations criteria provided, single submitter clinical testing A Heterozygous Nonsense variant c.1447C>T in Exon 6 of the CREBBP gene that results in the amino acid substitution p.Arg483* was identified. The observed variant is novel in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic (Variant ID: 458197). Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines.

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