Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002441702 | SCV002749245 | uncertain significance | Inborn genetic diseases | 2017-09-06 | criteria provided, single submitter | clinical testing | The p.P937L variant (also known as c.2810C>T), located in coding exon 14 of the CREBBP gene, results from a C to T substitution at nucleotide position 2810. The proline at codon 937 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in 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, |
RCV005019204 | SCV005645926 | likely benign | Rubinstein-Taybi syndrome due to CREBBP mutations; Menke-Hennekam syndrome 1 | 2024-02-08 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV005098299 | SCV005822685 | uncertain significance | Rubinstein-Taybi syndrome | 2024-09-16 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 937 of the CREBBP protein (p.Pro937Leu). This variant is present in population databases (rs766849648, gnomAD 0.006%). 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: 1796328). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CREBBP 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. |