Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000086121 | SCV003439804 | pathogenic | not provided | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 10 of the BEST1 protein (p.Ala10Val). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ala10 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9700209, 10854112, 25082885, 25174897). 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 BEST1 protein function. ClinVar contains an entry for this variant (Variation ID: 99709). This missense change has been observed in individuals with autosomal dominant Best vitelliform macular dystrophy (PMID: 10394929, 20381869, 31456290). This variant has been reported in individual(s) with autosomal recessive bestrophinopathy (PMID: 33039401); however, the role of the variant in this condition is currently unclear. This variant is not present in population databases (gnomAD no frequency). |
| Retina International | RCV000086121 | SCV000118265 | not provided | not provided | no assertion provided | not provided | ||
| Sharon lab, |
RCV001002886 | SCV001160919 | pathogenic | Vitelliform macular dystrophy 2 | 2019-06-23 | no assertion criteria provided | research |