ClinVar Miner

Submissions for variant NM_004380.3(CREBBP):c.6126G>T (p.Met2042Ile)

gnomAD frequency: 0.00001  dbSNP: rs1052723403
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001246005 SCV001419332 uncertain significance Rubinstein-Taybi syndrome 2022-07-25 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 sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2042 of the CREBBP protein (p.Met2042Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CREBBP-related conditions. ClinVar contains an entry for this variant (Variation ID: 970435).
Ambry Genetics RCV002357049 SCV002656994 uncertain significance Inborn genetic diseases 2019-01-08 criteria provided, single submitter clinical testing The p.M2042I variant (also known as c.6126G>T), located in coding exon 31 of the CREBBP gene, results from a G to T substitution at nucleotide position 6126. The methionine at codon 2042 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved through mammals but not in all available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002491828 SCV002782313 uncertain significance Rubinstein-Taybi syndrome due to CREBBP mutations; Menke-Hennekam syndrome 1 2022-02-05 criteria provided, single submitter clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001252201 SCV001427952 likely benign Intellectual disability 2019-01-01 no assertion criteria provided clinical testing

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