ClinVar Miner

Submissions for variant NM_004183.4(BEST1):c.73C>T (p.Arg25Trp) (rs281865214)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000086169 SCV001217537 pathogenic not provided 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 25 of the BEST1 protein (p.Arg25Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs281865214, ExAC 0.01%). This variant has been observed in individual(s) with autosomal dominant Best vitelliform macular dystrophy (PMID: 10854112, 20057903, 26201355, 23213274). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99751). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Arg25 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: PMID: 9700209, 23290749). 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.
Institute of Medical Molecular Genetics, University of Zurich RCV001352979 SCV001548062 likely pathogenic Vitelliform macular dystrophy type 2 2021-01-30 criteria provided, single submitter clinical testing
Retina International RCV000086169 SCV000118313 not provided not provided no assertion provided not provided

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