Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002879956 | SCV003640071 | uncertain significance | Inborn genetic diseases | 2022-09-06 | criteria provided, single submitter | clinical testing | The c.5962A>T (p.M1988L) alteration is located in exon 31 (coding exon 31) of the CREBBP gene. This alteration results from a A to T substitution at nucleotide position 5962, causing the methionine (M) at amino acid position 1988 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV005059349 | SCV005713700 | uncertain significance | Rubinstein-Taybi syndrome | 2024-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1988 of the CREBBP protein (p.Met1988Leu). 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: 2310619). 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) indicates that this missense variant is not expected to disrupt CREBBP protein function with a negative predictive value of 95%. 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. |