Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000086169 | SCV001217537 | pathogenic | not provided | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 25 of the BEST1 protein (p.Arg25Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with autosomal dominant Best vitelliform macular dystrophy (PMID: 10854112, 20057903, 23213274, 26201355). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99751). 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.Arg25 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9700209, 23290749). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Institute of Medical Molecular Genetics, |
RCV001352979 | SCV001548062 | likely pathogenic | Vitelliform macular dystrophy 2 | 2021-01-30 | criteria provided, single submitter | clinical testing | |
| Retina International | RCV000086169 | SCV000118313 | not provided | not provided | no assertion provided | not provided |