Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Blueprint Genetics | RCV001073527 | SCV001239074 | pathogenic | Retinal dystrophy | 2019-05-11 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000086187 | SCV001584641 | pathogenic | not provided | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 300 of the BEST1 protein (p.Glu300Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant Best vitelliform macular dystrophy (PMID: 10854112, 27078032, 28559085; Invitae). ClinVar contains an entry for this variant (Variation ID: 99768). 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%. Experimental studies have shown that this missense change does not substantially affect BEST1 function (PMID: 17110374). This variant disrupts the p.Glu300 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10331951, 13129869, 28559085). 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. |
| Retina International | RCV000086187 | SCV000118331 | not provided | not provided | no assertion provided | not provided |