Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000086196 | SCV001584642 | pathogenic | not provided | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 303 of the BEST1 protein (p.Asp303Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant Best vitelliform macular dystrophy (PMID: 12324875). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99777). 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.Asp303 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been observed in individuals with BEST1-related conditions (PMID: 21273940, 23213274; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Retina International | RCV000086196 | SCV000118340 | not provided | not provided | no assertion provided | not provided |