Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000606825 | SCV000712772 | likely pathogenic | Autosomal recessive bestrophinopathy | 2017-01-30 | criteria provided, single submitter | clinical testing | The p.Val505GlufsX9 (NM_004183.3 c.1514_1515delTG) variant in BEST1 has not been reported in the literature. This variant is predicted to cause a frameshift, wh ich alters the protein?s amino acid sequence beginning at position 505 and leads to a premature termination codon 9 amino acids downstream. This alteration is t hen predicted to lead to a truncated or absent protein. Biallelic loss of functi on of the BEST1 gene has been associated with autosomal recessive bestrophinopat hy. This variant has been identified in 3/121,356 of chromosomes by the Exome Ag gregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs752521456). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. In summary, alt hough additional studies are required to fully establish a null effect on the pr otein, the p.Val505GlufsX9 variant in BEST1 is likely pathogenic for bestrophin opathy in an autosomal recessive manner based upon its predicted functional impa ct. |
| Labcorp Genetics |
RCV001237913 | SCV001410700 | pathogenic | not provided | 2023-07-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 505511). This variant has not been reported in the literature in individuals affected with BEST1-related conditions. This variant is present in population databases (rs752521456, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Val505Glufs*9) in the BEST1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BEST1 are known to be pathogenic (PMID: 21825197). |
| Revvity Omics, |
RCV001237913 | SCV004238502 | likely pathogenic | not provided | 2023-06-13 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV004817816 | SCV005070005 | likely pathogenic | Retinal dystrophy | 2022-01-01 | criteria provided, single submitter | clinical testing |