Submissions for variant NM_001429.4(EP300):c.4756G>T (p.Ala1586Ser)

dbSNP: rs1480723806

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002573448	SCV002258197	uncertain significance	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	2021-03-27	criteria provided, single submitter	clinical testing	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 not expected to disrupt EP300 protein function. This sequence change replaces alanine with serine at codon 1586 of the EP300 protein (p.Ala1586Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with EP300-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
3billion, Medical Genetics	RCV004729008	SCV005329102	likely benign	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency; Colorectal cancer; Menke-Hennekam syndrome 2	2024-09-20	criteria provided, single submitter	clinical testing	The variant was identified in at least one patient who was diagnosed with a different variant in another gene and showed no symptoms related to the gene containing the variant in question.