Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Blueprint Genetics | RCV001073510 | SCV001239055 | likely pathogenic | Retinal dystrophy | 2019-04-25 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000086104 | SCV001410576 | pathogenic | not provided | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 80 of the BEST1 protein (p.Phe80Leu). 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: 25082885, 26201355). ClinVar contains an entry for this variant (Variation ID: 99695). 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 affects BEST1 function (PMID: 21878505). This variant disrupts the p.Phe80 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been observed in individuals with BEST1-related conditions (PMID: 21269699, 23213274), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Prevention |
RCV003398698 | SCV004119943 | pathogenic | BEST1-related condition | 2023-04-27 | criteria provided, single submitter | clinical testing | The BEST1 c.240C>A variant is predicted to result in the amino acid substitution p.Phe80Leu. This variant has been reported in the heterozygous state in individuals with Best vitelliform macular dystrophy (Lotery et al. 2000. PubMed ID: 10798642; Alapati et al. 2014. PubMed ID: 25082885; Katagiri et al. 2015. PubMed ID: 26201355). Alternate substitutions of this amino acid (p.Phe80Val and p.Phe80Cys) and the adjacent amino acid (p.Val81Met and p.Val81Leu) have also been reported in individuals with bestrophinopathies (Human Gene Mutation Database). This c.240C>A (p.Phe80Leu) variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Given the evidence, we interpret this variant as pathogenic. |
| Retina International | RCV000086104 | SCV000118248 | not provided | not provided | no assertion provided | not provided |