Submissions for variant NM_001429.4(EP300):c.4505C>T (p.Pro1502Leu)

dbSNP: rs1555911573

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000505247	SCV000830486	uncertain significance	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	2018-05-17	criteria provided, single submitter	clinical testing	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. 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 not been reported in the literature in individuals with EP300-related disease. ClinVar contains an entry for this variant (Variation ID: 438291). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 1502 of the EP300 protein (p.Pro1502Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine.
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV000505247	SCV000599260	likely pathogenic	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	2016-03-23	no assertion criteria provided	clinical testing