Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Diagnostic Laboratory, |
RCV001260706 | SCV001437798 | pathogenic | Intellectual disability | 2020-09-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000439427 | SCV001581591 | pathogenic | Rubinstein-Taybi syndrome due to EP300 haploinsufficiency | 2021-01-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with Rubinstein–Taybi syndrome (PMID: 27648933, 27465822). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 378053). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 1286 of the EP300 protein (p.Asn1286Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. |
Centogene AG - |
RCV000439427 | SCV002028307 | likely pathogenic | Rubinstein-Taybi syndrome due to EP300 haploinsufficiency | 2021-08-30 | criteria provided, single submitter | clinical testing | |
Gene |
RCV002244870 | SCV002513174 | pathogenic | not provided | 2022-05-09 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27465822, 32827181, 33644862, 27648933, 31785789) |
3billion | RCV000439427 | SCV002521376 | pathogenic | Rubinstein-Taybi syndrome due to EP300 haploinsufficiency | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.61; 3Cnet: 0.39). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000378053). The variant has been observed in at least two similarly affected unrelated individuals (PMID: 27465822, 32827181, 33644862). The variant has been previously reported as assumed (i.e. paternity and maternity not confirmed) de novo in at least one similarly affected unrelated individual (PMID: 27648933). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV002252119 | SCV002523993 | likely pathogenic | See cases | 2021-09-03 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS4, PM2, PM6 |
Preventiongenetics, |
RCV003401414 | SCV004103072 | pathogenic | EP300-related condition | 2023-08-20 | criteria provided, single submitter | clinical testing | The EP300 c.3857A>G variant is predicted to result in the amino acid substitution p.Asn1286Ser. This variant has been reported in multiple individuals with Rubinstein-Taybi syndrome and neurodevelopmental disorders; in most of these individuals, this variant was found to have arise de novo (Fergelot et al 2016. PubMed ID: 27648933; Hamilton MJ et al 2016. PubMed ID: 27465822; Table_S2, Turner TN et al 2019. PubMed ID: 31785789; Cross E et al 2020. PubMed ID: 32827181; Hiraide T et al 2021. PubMed ID: 33644862; Hamilton MJ et al 2016. PubMed ID: 27465822). 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 | RCV000439427 | SCV000513411 | pathogenic | Rubinstein-Taybi syndrome due to EP300 haploinsufficiency | 2019-02-26 | no assertion criteria provided | literature only | |
Wessex Regional Genetics Laboratory, |
RCV000439427 | SCV001189992 | likely pathogenic | Rubinstein-Taybi syndrome due to EP300 haploinsufficiency | 2019-11-05 | no assertion criteria provided | clinical testing |