Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002025760 | SCV002291465 | likely pathogenic | not provided | 2022-08-23 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 191 of the BEST1 protein (p.Leu191Pro). 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. ClinVar contains an entry for this variant (Variation ID: 1503856). This missense change has been observed in individuals with autosomal recessive bestrophinopathy (PMID: 17296903, 21809908, 31455904; Invitae). This variant has been reported in individual(s) with clinical features of autosomal dominant Best disease (PMID: 17296903; Invitae); however, the role of the variant in this condition is currently unclear. 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. Experimental studies have shown that this missense change affects BEST1 function (PMID: 24560797). |
Revvity Omics, |
RCV002025760 | SCV003827871 | likely pathogenic | not provided | 2021-12-30 | criteria provided, single submitter | clinical testing |