Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002536889 | SCV003439811 | pathogenic | not provided | 2022-05-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp312 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17898294, 18179881, 21330666, 22162627, 23290749). 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: 636003). This missense change has been observed in individual(s) with autosomal recessive bestrophinopathy (PMID: 21738390). It has also been observed to segregate with disease in related individuals. This variant has been reported in individual(s) with autosomal dominant Best vitelliform macular dystrophy (PMID: 30718709); however, the role of the variant in this condition is currently unclear. This variant is present in population databases (rs748351421, gnomAD 0.007%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 312 of the BEST1 protein (p.Asp312Glu). |
| Department of Clinical Genetics, |
RCV000787549 | SCV000926524 | likely pathogenic | Vitelliform macular dystrophy 2 | 2018-04-01 | no assertion criteria provided | research |