ClinVar Miner

Submissions for variant NM_004380.3(CREBBP):c.3517C>T (p.Arg1173Ter)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV003136570 SCV003819351 pathogenic not provided 2022-05-24 criteria provided, single submitter clinical testing
GeneDx RCV003136570 SCV004170078 pathogenic not provided 2023-10-11 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 17052327)
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV004594680 SCV005085904 pathogenic Rubinstein-Taybi syndrome due to CREBBP mutations 2024-09-20 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Menke-Hennekam syndrome 1 (MIM#618332) and Rubinstein-Taybi syndrome 1 (MIM#180849). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many NMD-predicted variants have previously been reported as pathogenic in patients with Rubinstein-Taybi syndrome (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported in three individuals with Rubinstein-Taybi syndrome, one of which is confirmed de novo (PMIDs: 17052327, 26788536, 31566936). (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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