Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000414599 | SCV000490524 | pathogenic | not provided | 2016-12-09 | criteria provided, single submitter | clinical testing | A pathogenic variant has been identified in the EP300 gene. The F1595V variant has been identified as a de novo variant with confirmed parentage in multiple unrelated individuals with developmental delay and dysmorphic features who were previously tested at GeneDx. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The F1595V variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts the F1595V variant is probably damaging to the protein structure/function. Therefore, the presence of this pathogenic variant is consistent with a diagnosis of Rubinstein-Taybi syndrome |
Ambry Genetics | RCV000624116 | SCV000740761 | likely pathogenic | Inborn genetic diseases | 2017-10-02 | criteria provided, single submitter | clinical testing | |
3billion | RCV000433095 | SCV002012257 | pathogenic | Rubinstein-Taybi syndrome due to EP300 haploinsufficiency | 2021-10-02 | criteria provided, single submitter | clinical testing | The variant has been previously reported as de novoo in a similarly affected individual (PMID: 27465822, PS2) The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.953, 3Cnet: 0.763, PP3). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Revvity Omics, |
RCV000414599 | SCV002022186 | pathogenic | not provided | 2021-08-31 | criteria provided, single submitter | clinical testing | |
Centogene AG - |
RCV000433095 | SCV002059456 | pathogenic | Rubinstein-Taybi syndrome due to EP300 haploinsufficiency | 2019-06-21 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000433095 | SCV003444488 | pathogenic | Rubinstein-Taybi syndrome due to EP300 haploinsufficiency | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1595 of the EP300 protein (p.Phe1595Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Rubinstein-Taybi syndrome (PMID: 27465822, 29133209). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 372363). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EP300 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003401394 | SCV004121049 | pathogenic | EP300-related condition | 2022-10-10 | criteria provided, single submitter | clinical testing | The EP300 c.4783T>G variant is predicted to result in the amino acid substitution p.Phe1595Val. This variant was reported to be a de novo event in multiple individuals with Rubinstein–Taybi syndrome (Table S3 - Retterer et al. 2016. PubMed ID: 26633542; Hamilton et al. 2016. PubMed ID: 27465822; Costain et al. 2017. PubMed ID: 29133209; Lecoquierre et al. 2019. PubMed ID: 31036916; Welters et al. 2019. PubMed ID: 31137009). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic. |
OMIM | RCV000433095 | SCV000513410 | pathogenic | Rubinstein-Taybi syndrome due to EP300 haploinsufficiency | 2019-02-26 | no assertion criteria provided | literature only | |
Costain lab, |
RCV000509054 | SCV000606780 | not provided | Multiple congenital anomalies | no assertion provided | clinical testing | ||
Molecular Genetics Laboratory, |
RCV000433095 | SCV000803699 | pathogenic | Rubinstein-Taybi syndrome due to EP300 haploinsufficiency | 2017-12-11 | no assertion criteria provided | clinical testing | |
Diagnostic Laboratory, |
RCV000414599 | SCV001978549 | likely pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000414599 | SCV001979660 | likely pathogenic | not provided | no assertion criteria provided | clinical testing |