Submissions for variant NM_004380.3(CREBBP):c.6673A>G (p.Met2225Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003052193	SCV003349450	uncertain significance	Rubinstein-Taybi syndrome	2022-11-15	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 CREBBP protein function. This variant has not been reported in the literature in individuals affected with CREBBP-related conditions. 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 2225 of the CREBBP protein (p.Met2225Val).
PreventionGenetics, part of Exact Sciences	RCV004725483	SCV005336800	uncertain significance	CREBBP-related disorder	2024-08-22	no assertion criteria provided	clinical testing	The CREBBP c.6673A>G variant is predicted to result in the amino acid substitution p.Met2225Val. 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.