Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002036610 | SCV002317640 | likely pathogenic | not provided | 2024-08-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 202 of the BEST1 protein (p.Arg202Gln). This variant is present in population databases (rs753437612, gnomAD 0.0009%). This variant has not been observed in the literature in individuals with autosomal recessive BEST1-related conditions. This variant has been reported in individual(s) with Stargardt macular dystrophy (PMID: 36259723); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 1525341). 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 BEST1 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg202 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21330666, 27519691, 31519547, 31766397). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |