Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001896617 | SCV002177077 | uncertain significance | Cerebral cavernous malformation 2 | 2023-07-16 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 186 of the CCM2 protein (p.Ala186Thr). This variant is present in population databases (rs758091168, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CCM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1400213). 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. |
| Ambry Genetics | RCV004041734 | SCV005029119 | uncertain significance | Inborn genetic diseases | 2023-11-26 | criteria provided, single submitter | clinical testing | The p.A186T variant (also known as c.556G>A), located in coding exon 5 of the CCM2 gene, results from a G to A substitution at nucleotide position 556. The alanine at codon 186 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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. |