ClinVar Miner

Submissions for variant NM_004183.4(BEST1):c.1514_1515del (p.Val505fs)

dbSNP: rs752521456
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized 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.
Invitae RCV001237913 SCV001410700 pathogenic not provided 2023-07-12 criteria provided, single submitter clinical testing 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). This variant is present in population databases (rs752521456, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with BEST1-related conditions. ClinVar contains an entry for this variant (Variation ID: 505511). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001237913 SCV004238502 likely pathogenic not provided 2023-06-13 criteria provided, single submitter clinical testing

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