Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000987493 | SCV001136796 | likely pathogenic | Bietti crystalline corneoretinal dystrophy | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001869345 | SCV002307103 | likely pathogenic | not provided | 2021-09-15 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg390 amino acid residue in CYP4V2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22087103, 26971461, 28051075). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt CYP4V2 protein function. ClinVar contains an entry for this variant (Variation ID: 802105). This variant has not been reported in the literature in individuals affected with CYP4V2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 390 of the CYP4V2 protein (p.Arg390Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. |