ClinVar Miner

Submissions for variant NM_001429.4(EP300):c.6680T>C (p.Met2227Thr)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003527348 SCV004370102 uncertain significance Rubinstein-Taybi syndrome due to EP300 haploinsufficiency 2023-05-15 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. 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 variant has not been reported in the literature in individuals affected with EP300-related conditions. This variant is present in population databases (rs374135370, gnomAD 0.002%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2227 of the EP300 protein (p.Met2227Thr).
GeneDx RCV005235722 SCV005882501 uncertain significance not provided 2024-09-06 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences RCV004738808 SCV005353078 uncertain significance EP300-related disorder 2024-05-15 no assertion criteria provided clinical testing The EP300 c.6680T>C variant is predicted to result in the amino acid substitution p.Met2227Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0016% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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