ClinVar Miner

Submissions for variant NM_001429.4(EP300):c.4933C>T (p.Arg1645Ter)

dbSNP: rs139310551
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ITMI RCV000162342 SCV000212644 pathogenic Rubinstein-Taybi syndrome due to EP300 haploinsufficiency 2015-03-09 criteria provided, single submitter research
Baylor Genetics RCV000162342 SCV001524098 pathogenic Rubinstein-Taybi syndrome due to EP300 haploinsufficiency 2019-08-28 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. The c.4933C>T (p.R1645*) variant is predicted to result in a premature stop codon in exon 30 of 31, at codon 1645 of 2414, and it has been previously reported in patients with Rubinstein-Taybi syndrome [PMID 27648933, 25712426]
Labcorp Genetics (formerly Invitae), Labcorp RCV000162342 SCV001583423 pathogenic Rubinstein-Taybi syndrome due to EP300 haploinsufficiency 2024-05-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1645*) in the EP300 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EP300 are known to be pathogenic (PMID: 15706485, 24476420). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of Rubinstein–Taybi syndrome (PMID: 25712426, 27648933). ClinVar contains an entry for this variant (Variation ID: 183678). For these reasons, this variant has been classified as Pathogenic.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV004551377 SCV004046234 pathogenic EP300-related disorder criteria provided, single submitter clinical testing This nonsense variant found in exon 30 of 31 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been previously reported as a heterozygous change in patients with Rubinstein-Taybi syndrome (PMID: 25712426, 27648933). The c.4933C>T (p.Arg1645Ter) variant is absent from the gnomAD population database and thus is presumed to be rare. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.4933C>T (p.Arg1645Ter) variant is classified as Pathogenic.
GeneDx RCV004719723 SCV005325863 pathogenic not provided 2023-11-13 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: 24476420, 30789376, 25712426, 27648933, 35904121)

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