Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003606499 | SCV004433872 | uncertain significance | Cerebral cavernous malformation 2 | 2023-02-01 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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 CCM2 protein function. This variant has not been reported in the literature in individuals affected with CCM2-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 226 of the CCM2 protein (p.Ile226Ser). |