Submissions for variant NM_001429.4(EP300):c.4235C>T (p.Ala1412Val)

gnomAD frequency: 0.00002  dbSNP: rs887226313

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003313239	SCV004012541	uncertain significance	not provided	2023-01-05	criteria provided, single submitter	clinical testing	Identified as paternally inherited in a patient with hepatoblastoma, craniosynostosis, facial dysmorphisms, and developmental delay. Patient also reported to have an additional variant in a known cancer predisposition gene (Aguiar et al., 2022); 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: 35495172)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003638822	SCV004448290	likely benign	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	2023-02-14	criteria provided, single submitter	clinical testing
Molecular Oncology - Human Genetics Lab, University of Sao Paulo	RCV001843903	SCV002103125	uncertain significance	Hepatoblastoma		no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV003401751	SCV004119858	uncertain significance	EP300-related disorder	2023-11-28	no assertion criteria provided	clinical testing	The EP300 c.4235C>T variant is predicted to result in the amino acid substitution p.Ala1412Val. This change was reported as a paternally inherited variant of uncertain significance in an individual with hepatoblastoma; however, no additional studies were done to assess its pathogenicity (Aguiar et al. 2022. PubMed ID: 35495172). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.