Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Blueprint Genetics | RCV001074078 | SCV001239647 | pathogenic | Retinal dystrophy | 2018-12-14 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001851592 | SCV002127963 | pathogenic | not provided | 2023-08-30 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant vitreoretinochoroidopathy (PMID: 15452077, 21072067, 26771239). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2744). 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 are conflicting or provide insufficient evidence to determine the effect of this variant on BEST1 function (PMID: 15452077). This variant disrupts the p.Val86 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). 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. This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 86 of the BEST1 protein (p.Val86Met). |
| OMIM | RCV000002867 | SCV000023025 | pathogenic | Autosomal dominant vitreoretinochoroidopathy | 2004-10-01 | no assertion criteria provided | literature only |