Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002885567 | SCV003242998 | uncertain significance | Cerebral cavernous malformation 2 | 2023-07-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 2037187). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 146 of the CCM2 protein (p.Arg146Trp). This variant is present in population databases (rs372613654, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CCM2-related conditions. 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 CCM2 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. |