Submissions for variant NM_001429.4(EP300):c.5866A>G (p.Met1956Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003639312	SCV004553556	uncertain significance	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	2023-08-17	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with EP300-related conditions. 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. 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1956 of the EP300 protein (p.Met1956Val).
PreventionGenetics, part of Exact Sciences	RCV004738880	SCV005346849	uncertain significance	EP300-related disorder	2024-07-08	no assertion criteria provided	clinical testing	The EP300 c.5866A>G variant is predicted to result in the amino acid substitution p.Met1956Val. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.